ArticlePloS one2016
GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 104 papers, 3 of them syntheses that pooled it.
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Who cites it
104 citing papers in PubMed, 3 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- Circulating Growth Differentiation Factor 15 (GDF15) in Paediatric Disease: A Systematic Review.Journal of cachexia, sarcopenia and muscle · 2025Pooled it
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Accuracy of FGF-21 and GDF-15 for the diagnosis of mitochondrial disorders: A meta-analysis.Annals of clinical and translational neurology · 2020Pooled it
- Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.The Journal of clinical investigation · 2021Trial
- Idebenone does not inhibit disability progression in primary progressive MS.Multiple sclerosis and related disorders · 2020Trial
- Mitochondrial dysfunction in neurology: biomarkers and clinical implications.Nature reviews. Neurology · 2026Review
- Context-specific hypermetabolism in humans with mitochondrial defects.Cell press blue · 2026Article
- From Pharmacodynamic Biomarker to Evaluating Treatment Response: Biomarkers in Primary Mitochondrial Diseases.Clinical and translational science · 2026Review
- Alterations in mitochondria and cellular senescence in aged sEH null female kidneys.GeroScience · 2026Article
- Growth differentiation factor 15: from stress response to clinical utility in chronic liver diseases.Journal of gastroenterology · 2026Review
- Molecular Bases of Myopathies and Their Impact on Clinical Practice: Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Cellular senescence in multiple sclerosis: hallmarks, immunosenescence, and therapeutic implications.Frontiers in immunology · 2026Review
- Mechanism of maternal gestational diabetes mellitus exacerbating myocardial injury in male offspring by upregulating growth differentiation factor 15 to promote mitochondrial dysfunction.Molecular and cellular biochemistry · 2026Article
- Examining saliva proteomic dynamics in mitochondrial diseases from a perspective of intrinsic health.Scientific reports · 2025Article
- Mitochondrial DNA Deletions and Plasma GDF-15 Protein Levels Are Linked to Hormonal Dysregulation and Multi-Organ Involvement in Female Reproductive Endocrine Disorders.Life (Basel, Switzerland) · 2025Article
- Evaluating the utility of growth differentiation factor 15 and fibroblast growth factor 21 as blood biomarkers for Rett syndrome.Scientific reports · 2025Article
- Interaction of PGC-1α and GDF15 in the stressed heart.Nature cardiovascular research · 2025Article
- Metabolic Messenger: growth differentiation factor 15.Nature metabolism · 2025Review
- Single large-scale mitochondrial DNA deletion syndromes: scientific and family conference optimizes the collection of rare disease research outcomes.Orphanet journal of rare diseases · 2025Article
- The mitochondrial disease biomarker GDF15 is dynamic, quantifiable in saliva, and correlates with disease severity.Molecular genetics and metabolism · 2025Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction.
methodsWe analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA.
resultsOur results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated.
conclusionsOur data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF-21 levels.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.