Mitochondrial complex I subunit MT-ND1 mutations affect disease progression. MT-ND1 is a core subunit of mitochondrial complex I, involved in its assembly and function. Mutations in MT-ND1 can disrupt complex I assembly, affect ubiquinone binding and proton transport, and impair oxidative phosphorylation, leading to various diseases. These mutations are associated with conditions such as Leber hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), type 2 diabetes (T2D), and other disorders. MT-ND1 mutations can also influence neurological, cardiovascular, and metabolic functions. The impact of MT-ND1 mutations on disease progression is influenced by factors such as heteroplasmy, nuclear gene interactions, and environmental factors. Research highlights the role of MT-ND1 in disease mechanisms and suggests potential diagnostic and therapeutic approaches, including targeting MT-ND1 mutations through gene therapy or biomarker-based strategies. Further studies are needed to fully understand the pathogenic mechanisms and develop effective treatments for diseases associated with MT-ND1 mutations.Mitochondrial complex I subunit MT-ND1 mutations affect disease progression. MT-ND1 is a core subunit of mitochondrial complex I, involved in its assembly and function. Mutations in MT-ND1 can disrupt complex I assembly, affect ubiquinone binding and proton transport, and impair oxidative phosphorylation, leading to various diseases. These mutations are associated with conditions such as Leber hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), type 2 diabetes (T2D), and other disorders. MT-ND1 mutations can also influence neurological, cardiovascular, and metabolic functions. The impact of MT-ND1 mutations on disease progression is influenced by factors such as heteroplasmy, nuclear gene interactions, and environmental factors. Research highlights the role of MT-ND1 in disease mechanisms and suggests potential diagnostic and therapeutic approaches, including targeting MT-ND1 mutations through gene therapy or biomarker-based strategies. Further studies are needed to fully understand the pathogenic mechanisms and develop effective treatments for diseases associated with MT-ND1 mutations.