ArticleHuman molecular genetics2018
USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase.Physiological research · 2024Pooled it
- Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation.Science advances · 2026Article
- Mitochondrial remodeling in skeletal muscle underlies exercise-induced reversal of age-associated functional decline in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular machineries shaping the mitochondrial inner membrane.Nature reviews. Molecular cell biology · 2025Review
- Expanding the Allelic and Clinical Heterogeneity of Movement Disorders Linked to Defects of Mitochondrial Adenosine Triphosphate Synthase.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- A New Perspective on the Role of Alterations in Mitochondrial Proteins Involved in ATP Synthesis and Mobilization in Cardiomyopathies.International journal of molecular sciences · 2025Review
- The fourth family in the world with a novel variant in the ATP5MK gene: four siblings with complex V (ATP synthase) deficiency.Neurogenetics · 2025Article
- Integrative multi-omics analysis unveils the connection between transcriptomic characteristics associated with mitochondria and the tumor immune microenvironment in lower-grade gliomas.Scientific reports · 2024Article
- The Whole Genome DNA Methylation Signatures of Hindlimb Muscles in Chinese Alligators during Hibernation and Active Periods.Animals : an open access journal from MDPI · 2024Article
- Article
- ATP synthase interactome analysis identifies a new subunit l as a modulator of permeability transition pore in yeast.Scientific reports · 2023Article
- Next-generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment.Bioscience reports · 2022Article
- From the Structural and (Dys)Function of ATP Synthase to Deficiency in Age-Related Diseases.Life (Basel, Switzerland) · 2022Review
- Variants in Mitochondrial ATP Synthase Cause Variable Neurologic Phenotypes.Annals of neurology · 2022Article
- Molecular Genetics Overview of Primary Mitochondrial Myopathies.Journal of clinical medicine · 2022Review
- Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth.Cell reports · 2022Article
- The ATPase Inhibitory Factor 1 is a Tissue-Specific Physiological Regulator of the Structure and Function of Mitochondrial ATP Synthase: A Closer Look Into Neuronal Function.Frontiers in physiology · 2022Review
- A revised model for mitochondrial dysfunction in Duchenne muscular dystrophy.European journal of translational myology · 2021Article
- Downregulation by CNNM2 of ATP5MD expression in the 10q24.32 schizophrenia-associated locus involved in impaired ATP production and neurodevelopment.NPJ schizophrenia · 2021Article
- The ATP Synthase Deficiency in Human Diseases.Life (Basel, Switzerland) · 2021Review
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22 authors at 6 institutions in 1 country.
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Abstract
Leigh syndrome is a frequent, heterogeneous pediatric presentation of mitochondrial oxidative phosphorylation (OXPHOS) disease, manifesting with psychomotor retardation and necrotizing lesions in brain deep gray matter. OXPHOS occurs at the inner mitochondrial membrane through the integrated activity of five protein complexes, of which complex V (CV) functions in a dimeric form to directly generate adenosine triphosphate (ATP). Mutations in several different structural CV subunits cause Leigh syndrome; however, dimerization defects have not been associated with human disease. We report four Leigh syndrome subjects from three unrelated Ashkenazi Jewish families harboring a homozygous splice-site mutation (c.87 + 1G>C) in a novel CV subunit disease gene, USMG5. The Ashkenazi population allele frequency is 0.57%. This mutation produces two USMG5 transcripts, wild-type and lacking exon 3. Fibroblasts from two Leigh syndrome probands had reduced wild-type USMG5 mRNA expression and undetectable protein. The mutation did not alter monomeric CV expression, but reduced both CV dimer expression and ATP synthesis rate. Rescue with wild-type USMG5 cDNA in proband fibroblasts restored USMG5 protein, increased CV dimerization and enhanced ATP production rate. These data demonstrate that a recurrent USMG5 splice-site founder mutation in the Ashkenazi Jewish population causes autosomal recessive Leigh syndrome by reduction of CV dimerization and ATP synthesis.
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