ArticleThe EMBO journal2020
Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Clinical and modifier gene profiles in reversible infantile respiratory chain deficiency: three Chinese cases report and literature review.Translational pediatrics · 2026Article
- Identification of Nuclear Genetic Loci Linked to Clinical Features of the m.3243A>G Mitochondrial DNA Variant.Neurology. Genetics · 2026Article
- Txnrd2 loss in skeletal muscle causes muscle atrophy and drives leanness and obesity resistance.Redox biology · 2026Article
- Modifier variants in metabolic pathways are associated with an increased penetrance of Leber's Hereditary Optic Neuropathy.European journal of human genetics : EJHG · 2026Article
- Mitochondrial damage is associated with an early immune response in inclusion body myositis.Brain : a journal of neurology · 2025Article
- PDE12 mediated pruning of the poly-A tail of mitochondrial DNA-encoded tRNAs is essential for survival.EMBO molecular medicine · 2025Article
- DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy.The EMBO journal · 2024Article
- Illuminating mitochondrial translation through mouse models.Human molecular genetics · 2024Review
- Digenic Inheritance in Rare Disorders and Mitochondrial Disease-Crossing the Frontier to a More Comprehensive Understanding of Etiology.International journal of molecular sciences · 2024Review
- DELE1 promotes translation-associated homeostasis, growth, and survival in mitochondrial myopathy.bioRxiv : the preprint server for biology · 2024Article
- Multi-level profiling unravels mitochondrial dysfunction in myotonic dystrophy type 2.Acta neuropathologica · 2024Article
- A clinical approach to diagnosis and management of mitochondrial myopathies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Interactions of mitochondrial and skeletal muscle biology in mitochondrial myopathy.The Biochemical journal · 2023Review
- Impoverished Conceptions of Gene Causation and Therapy in Developmental Neurology.Pediatric neurology · 2023Review
- Use of dual genomic sequencing to screen mitochondrial diseases in pediatrics: a retrospective analysis.Scientific reports · 2023Article
- Lactate metabolism is essential in early-onset mitochondrial myopathy.Science advances · 2023Article
- Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study.Scientific reports · 2022Observational
- OMA1 mediates local and global stress responses against protein misfolding in CHCHD10 mitochondrial myopathy.The Journal of clinical investigation · 2022Article
- Expression pattern of mitochondrial respiratory chain enzymes in skeletal muscle of patients with mitochondrial myopathy associated with the homoplasmic m.14674T>C variant.Brain pathology (Zurich, Switzerland) · 2022Article
- Frataxin deficiency lowers lean mass and triggers the integrated stress response in skeletal muscle.JCI insight · 2022Article
Corrections and comments
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Authors and funding
38 authors at 17 institutions in 10 countries.
Funding
Abstract
Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only ~ 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.
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Registered trials
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