ArticleNeurology2016
FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders.
Open access · bronzeAbstract readValidation Study
In one paragraph
Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 2 pooled it
9.7field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
133 citing papers in PubMed, 2 syntheses or guidelines pooled it, 216 citations in OpenAlex.
- A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum.Diagnostics (Basel, Switzerland) · 2024Guideline
- Exploring the correlation between serum fibroblast growth factor-21 levels and Sarcopenia: a systematic review and meta-analysis.BMC musculoskeletal disorders · 2023Pooled it
- Trial
- Mitochondrial dysfunction in neurology: biomarkers and clinical implications.Nature reviews. Neurology · 2026Review
- Mitochondrial Quality Control in Inherited Mitochondrial Cardiomyopathy: Convergent Pathobiology and a Testable Therapeutic Framework.International journal of molecular sciences · 2026Review
- Cumulative and Interactive Effects of Heavy Metal Mixtures Across Neurodegenerative Diseases: A Comparative Review of Alzheimer, Parkinson, Amyotrophic Lateral Sclerosis and Multiple Sclerosis.Journal of xenobiotics · 2026Review
- Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions.Biogerontology · 2026Review
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- Late-onset severe axonal polyneuropathy in mut0 methylmalonic acidemia after liver-kidney transplantation: a genotype-informed case report.BMC neurology · 2026Article
- From Pharmacodynamic Biomarker to Evaluating Treatment Response: Biomarkers in Primary Mitochondrial Diseases.Clinical and translational science · 2026Review
- Screening and Stratification Utility of GDF-15 and FGF-21 in Individuals Evaluated for Suspected Mitochondrial Disease: A Malaysian Cohort Study.Metabolites · 2026Article
- Non-invasive biomarkers for diagnosis and monitoring of primary mitochondrial diseases.Journal of neurology · 2026Review
- Mitochondrial Dysfunction in Propionic Acidemia: A Case-Report and Review of the Literature.JIMD reports · 2026Article
- Growth differentiation factor 15: from stress response to clinical utility in chronic liver diseases.Journal of gastroenterology · 2026Review
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- Adaptive mechanisms in pancreatic islets counteract mitochondrial dysfunction in Barth syndrome.Diabetologia · 2026Article
- Mitochondrial and psychosocial stress-related regulation of FGF21 in humans.Nature metabolism · 2025Article
- Evaluating the utility of growth differentiation factor 15 and fibroblast growth factor 21 as blood biomarkers for Rett syndrome.Scientific reports · 2025Article
- Evaluation of Serum FGF21 Levels in Patients with Mitochondrial Aminoacyl-tRNA Synthetase Deficiency.International journal of molecular sciences · 2025Article
- A two-strata energy flux system driven by a stress hormone prioritizes cardiac energetics.Signal transduction and targeted therapy · 2025Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 1 institution in 1 country.
Jenni M LehtonenFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Saara ForsströmFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Emanuela BottaniFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Carlo ViscomiFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Olivier R BarisFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Helena IsoniemiFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Krister HöckerstedtFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Pia ÖsterlundFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Mikko HurmeFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Juulia JylhäväFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Sirpa LeppäFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Ritva MarkkulaFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Tiina HeliöFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Giuliana MombelliFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Johanna UusimaaFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Reijo LaaksonenFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Hannu LaaksovirtaFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Mari AuranenFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Massimo ZevianiFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Jan SmeitinkFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Rudolf J WiesnerFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Kazuto NakadaFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Pirjo IsohanniFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland.
Anu SuomalainenFrom the Research Programs Unit, Molecular Neurology (J.M.L., S.F., H.L., M.A., P.I.), Faculty of Medicine/Clinicum, Oncology (P.O.), and Finland Genome Scale Biology Program (S.L.), University of Helsinki, Finland; Mitochondrial Medicine Group (E.B., C.V., M.Z.), Medical Research Council Mitochondrial Biology Unit, Cambridge, UK; Center for Physiology and Pathophysiology (O.R.B., R.J.W.), Institute of Vegetative Physiology, University of Köln, Germany; Transplantation and Liver Surgery Clinic (H.I., K.H.), Department of Oncology (P.O., S.L.), and Heart and Lung Center, Department of Cardiology (T.H.), Helsinki University Hospital; School of Medicine (M.H., J.J., R.L.), University of Tampere; Anaesthesiology, Intensive Care and Pain Medicine (R.M.), Clinical Neurosciences, Neurology (H.L., M.A., A.S.), and Child Neurology, Children's Hospital (P.I.), University of Helsinki and Helsinki University Hospital, Finland; Dyslipidemia Center (G.M.), Cardiotoracovascular Department, Niguarda Hospital, Milan, Italy; PEDEGO Research Unit (J.U.) and Biocenter Oulu (J.U.), University of Oulu; Finnish Clinical Biobank Tampere (R.L.), Tampere University Hospital, Finland; Nijmegen Centre for Mitochondrial Disorders (J.S.), Radboud University Medical Centre, Nijmegen, the Netherlands; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) (R.J.W.), Köln; Center for Molecular Medicine Cologne (R.J.W.), CMMC, University of Köln, Germany; Faculty of Life and Environmental Sciences (K.N.), University of Tsukuba, Japan; and Medical Research Center Oulu (J.U.), Oulu University Hospital and University of Oulu, Finland. anu.wartiovaara@helsinki.fi.
MRC Mitochondrial Biology Unit · GB
Funding
Medical Research Council MC_UP_1002/1
Abstract
objectiveTo validate new mitochondrial myopathy serum biomarkers for diagnostic use.
methodsWe analyzed serum FGF21 (S-FGF21) and GDF15 from patients with (1) mitochondrial diseases and (2) nonmitochondrial disorders partially overlapping with mitochondrial disorder phenotypes. We (3) did a meta-analysis of S-FGF21 in mitochondrial disease and (4) analyzed S-Fgf21 and skeletal muscle Fgf21 expression in 6 mouse models with different muscle-manifesting mitochondrial dysfunctions.
resultsWe report that S-FGF21 consistently increases in primary mitochondrial myopathy, especially in patients with mitochondrial translation defects or mitochondrial DNA (mtDNA) deletions (675 and 347 pg/mL, respectively; controls: 66 pg/mL, p < 0.0001 for both). This is corroborated in mice (mtDNA deletions 1,163 vs 379 pg/mL, p < 0.0001). However, patients and mice with structural respiratory chain subunit or assembly factor defects showed low induction (human 335 pg/mL, p < 0.05; mice 335 pg/mL, not significant). Overall specificities of FGF21 and GDF15 to find patients with mitochondrial myopathy were 89.3% vs 86.4%, and sensitivities 67.3% and 76.0%, respectively. However, GDF15 was increased also in a wide range of nonmitochondrial conditions.
conclusionsS-FGF21 is a specific biomarker for muscle-manifesting defects of mitochondrial translation, including mitochondrial transfer-RNA mutations and primary and secondary mtDNA deletions, the most common causes of mitochondrial disease. However, normal S-FGF21 does not exclude structural respiratory chain complex or assembly factor defects, important to acknowledge in diagnostics. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that elevated S-FGF21 accurately distinguishes patients with mitochondrial myopathies from patients with other conditions, and FGF21 and GDF15 mitochondrial myopathy from other myopathies.
Indexed as
AdultAged, 80 and overAnimalsBiomarkersDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleFibroblast Growth FactorsGrowth Differentiation Factor 15HumansMaleMice, TransgenicMiddle AgedMitochondrial DiseasesMuscle, SkeletalMutationBiomarkersfibroblast growth factor 21Fibroblast Growth FactorsGDF15 protein, humanGrowth Differentiation Factor 15RNA, Fungal
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