ArticleMitochondrion2021
Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.
Article in Mitochondrion, 2021. 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, 42 citations in OpenAlex.
- Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.European journal of haematology · 2026Review
- NDUFA5 deficiency promotes renal inflammation in diabetic nephropathy via mitochondrial ROS signaling.iScience · 2026Article
- Refining antibiotic cocktail regimens for pseudo-germ-free mice and their impact on gut microbiome and pancreatic tumor proteomics.Journal of advanced research · 2026Article
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Mitochondria-Related Pathogenic Genes in Paediatric Asthma: A Multi-Omics Mendelian Randomization Study.Journal of cellular and molecular medicine · 2026Article
- NGR1 Ameliorates Hepatocyte Steatosis and Mitochondrial Dysfunction Associated with the Restoration of NDUFS2.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Transcriptomic Identification and Validation of NDUFS2 in Acute Rat TMJ Synovitis and Its Functional Role in LPS-Induced Synovial Fibroblast Inflammation.Journal of inflammation research · 2026Article
- Multi-omics Analysis of Energy Metabolism Pathways Across Major Psychiatric Disorders.Molecular neurobiology · 2025Article
- A multi-omics prognostic model of cuproptosis affects the prognosis of stomach adenocarcinoma.Clinical epigenetics · 2025Article
- Disulfidptosis in pediatric AML: a multi-omics approach to risk stratification and potential therapeutic strategy.Cancer cell international · 2025Article
- Molecular Alterations in Core Subunits of Mitochondrial Complex I and Their Relation to Parkinson's Disease.Molecular neurobiology · 2025Review
- Rotenone adaptation promotes migration and invasion of p53-wild-type colon cancer through lipid metabolism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.Molecular neurobiology · 2025Article
- An integrated investigation of mitochondrial genes in COPD reveals the causal effect of NDUFS2 by regulating pulmonary macrophages.Biology direct · 2025Article
- Single-nucleus transcriptomics reveals time-dependent and cell-type-specific effects of psilocybin on gene expression.bioRxiv : the preprint server for biology · 2025Article
- Hino-Fe Chelate Suppresses Osteosarcoma Progression through Dual Induction of Ferroptosis and NLRC4-mediated Pyroptosis: Mechanisms and Therapeutic Implications.International journal of biological sciences · 2025Article
- The Effect of Mulberry Silage Supplementation on the Carcass Fatness and Long-Chain Fatty Acid Composition of Growing Lambs Compared with Traditional Corn Silage.Foods (Basel, Switzerland) · 2024Article
- The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.Aging cell · 2024Article
- ACACA reduces lipid accumulation through dual regulation of lipid metabolism and mitochondrial function via AMPK- PPARα- CPT1A axis.Journal of translational medicine · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Complex I is the largest and most intricate of the protein complexes of mitochondrial electron transport chain (ETC). This L-shaped enzyme consists of a peripheral hydrophilic matrix domain and a membrane-bound orthogonal hydrophobic domain. The interfacial region between these two arms is known to be critical for binding of ubiquinone moieties and has also been shown to be the binding site of Complex I inhibitors. Knowledge on specific roles of the ETC interfacial region proteins is scarce due to lack of knockout cell lines and animal models. Here we mutated nuclear encoded NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUFS2), one of three protein subunits of the interfacial region, in a human embryonic kidney cell line 293 using a CRISPR/Cas9 procedure. Disruption of NDUFS2 significantly decreased cell growth in medium, Complex I specific respiration, glycolytic capacity, ATP pool and cell-membrane integrity, but significantly increased Complex II respiration, ROS generation, apoptosis, and necrosis. Treatment with idebenone, a clinical benzoquinone currently being investigated in other indications, partially restored growth, ATP pool, and oxygen consumption of the mutant. Overall, our results suggest that NDUFS2 is vital for growth and metabolism of mammalian cells, and respiratory defects of NDUFS2 dysfunction can be partially corrected with treatment of an established mitochondrial therapeutic candidate. This is the first report to use CRISPR/Cas9 approach to construct a knockout NDUFS2 cell line and use the constructed mutant to evaluate the efficacy of a known mitochondrial therapeutic to enhance bioenergetic capacity.
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