ArticleAmerican journal of human genetics2009
The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency.
Article in American journal of human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 137 citations in OpenAlex.
- ALR couples IMS redox and heme biosynthesis beyond the disulfide relay.Science advances · 2026Article
- Biallelic variants in CHCHD4 are associated with combined OXPHOS defect leading to mitochondrial disease.HGG advances · 2026Article
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- The Role and Research Progress of Mitochondria in Sensorineural Hearing Loss.Molecular neurobiology · 2025Review
- Oxidative protein folding in the intermembrane space of human mitochondria.FEBS open bio · 2024Review
- Dual diagnosis ofRare (Amsterdam, Netherlands) · 2024Article
- Polymorphism rs1046495 of the GFER Gene as a New Genetic Marker of Preposition to Type 2 Diabetes Mellitus.Bulletin of experimental biology and medicine · 2022Article
- The protective roles of augmenter of liver regeneration in hepatocytes in the non-alcoholic fatty liver disease.Frontiers in pharmacology · 2022Review
- Review
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration.Life (Basel, Switzerland) · 2021Review
- Article
- The mitochondrial intermembrane space: the most constricted mitochondrial sub-compartment with the largest variety of protein import pathways.Open biology · 2021Review
- CHCHD4 (MIA40) and the mitochondrial disulfide relay system.Biochemical Society transactions · 2021Review
- The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases.Genes · 2021Review
- Article
- Redox-Mediated Regulation of Mitochondrial Biogenesis, Dynamics, and Respiratory Chain Assembly in Yeast and Human Cells.Frontiers in cell and developmental biology · 2021Review
- Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation.Frontiers in cell and developmental biology · 2021Article
- Effects of Liposome and Cardiolipin on Folding and Function of Mitochondrial Erv1.International journal of molecular sciences · 2020Article
- Mitochondrial diseases: expanding the diagnosis in the era of genetic testing.Journal of translational genetics and genomics · 2020Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
A disulfide relay system (DRS) was recently identified in the yeast mitochondrial intermembrane space (IMS) that consists of two essential components: the sulfhydryl oxidase Erv1 and the redox-regulated import receptor Mia40. The DRS drives the import of cysteine-rich proteins into the IMS via an oxidative folding mechanism. Erv1p is reoxidized within this system, transferring its electrons to molecular oxygen through interactions with cytochrome c and cytochrome c oxidase (COX), thereby linking the DRS to the respiratory chain. The role of the human Erv1 ortholog, GFER, in the DRS has been poorly explored. Using homozygosity mapping, we discovered that a mutation in the GFER gene causes an infantile mitochondrial disorder. Three children born to healthy consanguineous parents presented with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. The consequences of the mutation at the level of the patient's muscle tissue and fibroblasts were 1) a reduction in complex I, II, and IV activity; 2) a lower cysteine-rich protein content; 3) abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and 4) accelerated time-dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces cerevisiae erv1(R182H) mutant strain reproduced the complex IV activity defect and exhibited genetic instability of the mtDNA and mitochondrial morphological defects. These findings shed light on the mechanisms of mitochondrial biogenesis, establish the role of GFER in the human DRS, and promote an understanding of the pathogenesis of a new mitochondrial disease.
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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.