ArticleProceedings of the National Academy of Sciences of the United States of America2015
Accessory NUMM (NDUFS6) subunit harbors a Zn-binding site and is essential for biogenesis of mitochondrial complex I.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 84 citations in OpenAlex.
- Article
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- Unveiling Moxibustion's Impact on AD Mice Learning and Memory: Role of Mitochondrial Respiratory Chain Complex I Subunit in the Hippocampus.Molecular neurobiology · 2025Article
- Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency.Cell death discovery · 2025Article
- The human zinc-binding cysteine proteome.Cell · 2025Article
- Proteomics analysis in rats reveals convergent mechanisms between major depressive disorder and dietary zinc deficiency.Pharmacological reports : PR · 2025Article
- Insights into Molecular Mechanisms of Anticancer Activity ofPlants (Basel, Switzerland) · 2024Article
- Alternative splicing expands the clinical spectrum of NDUFS6-related mitochondrial disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Using cryo-EM to understand the assembly pathway of respiratory complex I.Acta crystallographica. Section D, Structural biology · 2024Article
- Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.Advanced pharmaceutical bulletin · 2024Review
- Eleven Crucial Pesticides Appear to Regulate Key Genes That Link MPTP Mechanism to Cause Parkinson's Disease through the Selective Degeneration of Dopamine Neurons.Brain sciences · 2023Article
- Insights into complex I assembly: Function of NDUFAF1 and a link with cardiolipin remodeling.Science advances · 2022Article
- Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke.Frontiers of medicine · 2022Article
- Extensive mitochondrial proteome disturbance occurs during the early stages of acute myocardial ischemia.Experimental and therapeutic medicine · 2022Article
- Mitochondrial iron-sulfur clusters: Structure, function, and an emerging role in vascular biology.Redox biology · 2021Review
- Cheminformatic quantum mechanical enzyme model design: A catechol-O-methyltransferase case study.Biophysical journal · 2021Article
- A ferredoxin bridge connects the two arms of plant mitochondrial complex I.The Plant cell · 2021Article
- Accessory Subunits of the Matrix Arm of Mitochondrial Complex I with a Focus on Subunit NDUFS4 and Its Role in Complex I Function and Assembly.Life (Basel, Switzerland) · 2021Review
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial proton-pumping NADH:ubiquinone oxidoreductase (respiratory complex I) comprises more than 40 polypeptides and contains eight canonical FeS clusters. The integration of subunits and insertion of cofactors into the nascent complex is a complicated multistep process that is aided by assembly factors. We show that the accessory NUMM subunit of complex I (human NDUFS6) harbors a Zn-binding site and resolve its position by X-ray crystallography. Chromosomal deletion of the NUMM gene or mutation of Zn-binding residues blocked a late step of complex I assembly. An accumulating assembly intermediate lacked accessory subunit N7BM (NDUFA12), whereas a paralog of this subunit, the assembly factor N7BML (NDUFAF2), was found firmly bound instead. EPR spectroscopic analysis and metal content determination after chromatographic purification of the assembly intermediate showed that NUMM is required for insertion or stabilization of FeS cluster N4.
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