ArticleNature2016
Accessory subunits are integral for assembly and function of human mitochondrial complex I.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 344 papers, 1 of them a synthesis that pooled it.
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Who cites it
344 citing papers in PubMed, 1 synthesis or guideline pooled it, 647 citations in OpenAlex.
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- TRPA1 deficiency alters brown adipose tissue proteome and thermogenic gene expression during cold exposure in mice.Biochemistry and biophysics reports · 2026Article
- Adaptation of OXPHOS biogenesis to cellular requirements.Protein science : a publication of the Protein Society · 2026Review
- Mitochondrial Genomic Alterations in Pediatric Acute Lymphoblastic Leukemia: Implications for Methotrexate-Induced Neurotoxicity and Ethnic Disparities.Cancer medicine · 2026Article
- Hypoxia rescues complex 1-associated disease caused by proteostatic defects.Nature metabolism · 2026Article
- The Disease Gene THAP12 is a Transcriptional Regulator of Mitochondrial ETC Complex I.bioRxiv : the preprint server for biology · 2026Article
- A multi-omics approach investigating thrombolysis resistance in acute ischemic stroke thrombi.Journal of thrombosis and thrombolysis · 2026Article
- Electron transport chain complex I and mitochondrial fusion regulate ROS for differentiation in Drosophila neural stem cells.Stem cell reports · 2026Article
- Electron tomography reveals mitochondrial network and cristae remodelling during cell differentiation in the human placenta.Nature communications · 2026Article
- Recessive variants in mitochondrial complex I nuclear subunits are an underrated cause of optic atrophy.Brain : a journal of neurology · 2026Article
- Loss of heterozygosity exposes germline mutations in complex I and drives Warburg metabolism in oncocytic carcinoma of the thyroid.Science advances · 2026Article
- Identification of respiratory chain complex I deficiency due toGenes & diseases · 2026Article
- Article
- Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 2026Review
- Prolonged linezolid therapy induces progressive mitochondrial dysfunction in human peripheral blood mononuclear cells.Journal of translational medicine · 2026Article
- Identification of novel NDUFA3 variants in a patient with mitochondrial disorders.Pediatric research · 2026Article
- Mitochondrial dysfunction triggers a maladaptive peroxisomal response driving lipid accumulation.Redox biology · 2026Article
- Targeting the Mitochondrial Phenotype in Cockayne Syndrome Patient Cells: From Bioenergetic Fragility to Pharmacologic Rescue.bioRxiv : the preprint server for biology · 2026Article
284 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson's disease and ageing. Bacterial and human complex I share 14 core subunits that are essential for enzymatic function; however, the role and necessity of the remaining 31 human accessory subunits is unclear. The incorporation of accessory subunits into the complex increases the cellular energetic cost and has necessitated the involvement of numerous assembly factors for complex I biogenesis. Here we use gene editing to generate human knockout cell lines for each accessory subunit. We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability. Quantitative proteomic analysis of cell lines revealed that loss of each subunit affects the stability of other subunits residing in the same structural module. Analysis of proteomic changes after the loss of specific modules revealed that ATP5SL and DMAC1 are required for assembly of the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with proteomics represents a powerful tool for dissecting large multi-subunit complexes and enables the study of complex dysfunction at a cellular level.
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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.