{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNDUFV2 encodes a core nuclear‐encoded subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase), which is essential for transferring electrons from NADH to ubiquinone in the respiratory chain. Disruption of this protein—whether through splice‐site mutations, deletions, or missense variants—can compromise complex I assembly and function, leading to markedly decreased protein levels. Such functional impairments have been associated with complex I deficiencies underlying clinical conditions such as early-onset hypertrophic cardiomyopathy and encephalopathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its fundamental role in cellular energy production, altered expression and sequence variation of NDUFV2 have been implicated in various neuropsychiatric disorders. Multiple studies have shown that genetic polymorphisms in the promoter or coding regions of NDUFV2 and consequent changes in mRNA and protein levels are associated with an increased risk of bipolar disorder and schizophrenia, with some findings extending to Parkinson’s disease. These observations support the notion that mitochondrial dysfunction affecting complex I—potentially through modified NDUFV2 activity—may contribute to the pathophysiology of these conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in bioenergetics and neuropsychiatric disease, NDUFV2 has been found to exert additional regulatory effects in diverse tissues. In adipose tissue, for instance, up-regulation of Ndufv2 can enhance mitochondrial supercomplex assembly and elevate reactive oxygen species production, thereby stimulating mitochondrial biogenesis and linking its expression to metabolic traits. Furthermore, aberrant overexpression of NDUFV2 has been associated with unfavorable prognoses in prostate cancer, and genetic polymorphisms in this gene have even been implicated in conditions such as lumbar disc degeneration. Intriguingly, regulatory influences by a related pseudogene (NDUFV2P1) have also been shown to impact NDUFV2 protein levels and complex I-driven respiration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paule Bénit, Réjane Beugnot, Dominique Chretien, et al. 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