ArticleBMC genomics2014
Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies.
Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02745938 (GDF-15 as a Biomarker for Mitochondrial Disease), which is not on this map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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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.
GDF-15 as a Biomarker for Mitochondrial Disease
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Accuracy of FGF-21 and GDF-15 for the diagnosis of mitochondrial disorders: A meta-analysis.Annals of clinical and translational neurology · 2020Pooled it
- Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans.Frontiers in endocrinology · 2026Trial
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- From Pharmacodynamic Biomarker to Evaluating Treatment Response: Biomarkers in Primary Mitochondrial Diseases.Clinical and translational science · 2026Review
- Non-invasive biomarkers for diagnosis and monitoring of primary mitochondrial diseases.Journal of neurology · 2026Review
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Metabolic Messenger: growth differentiation factor 15.Nature metabolism · 2025Review
- The mitochondrial disease biomarker GDF15 is dynamic, quantifiable in saliva, and correlates with disease severity.Molecular genetics and metabolism · 2025Article
- Growth differentiation factor 15: a valuable biomarker for the diagnosis and prognosis of late-onset form of multiple Acyl-CoA dehydrogenation deficiency.Orphanet journal of rare diseases · 2025Article
- Central mechanisms of emesis: A role for GDF15.Neurogastroenterology and motility · 2025Review
- The emerging role of growth differentiation factor 15 as a potential disease biomarker in juvenile dermatomyositis.Rheumatology (Oxford, England) · 2025Article
- GDF15 associates with, but is not responsible for, exercise-induced increases in corticosterone and indices of lipid utilization in mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy.The EMBO journal · 2024Article
- Eliminating elevated p53 signaling fails to rescue skeletal muscle defects or extend survival in lamin A/C-deficient mice.Cell death discovery · 2024Article
- Pathophysiological roles of the serum acylcarnitine level and acylcarnitine/free carnitine ratio in patients with cardiovascular diseases.International journal of cardiology. Heart & vasculature · 2024Article
- DELE1 promotes translation-associated homeostasis, growth, and survival in mitochondrial myopathy.bioRxiv : the preprint server for biology · 2024Article
- Characterization of methionine dependence in melanoma cells.Molecular omics · 2024Article
- Biomarkers of mitochondrial disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Septic Cardiomyopathy.Reviews in cardiovascular medicine · 2024Review
- Red Flags in Primary Mitochondrial Diseases: What Should We Recognize?International journal of molecular sciences · 2023Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 11 institutions in 4 countries.
Funding
Abstract
backgroundMutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays.
resultsWe have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression.
conclusionOur data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required.
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Registered trials
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.