Genetic aberration analysis of mitochondrial respiratory complex I implications in the development of neurological disorders and their clinical significance

Growing neurological diseases pose difficult challenges for modern medicine to diagnose and manage them effectively. Many neurological disorders mainly occur due to genetic alteration in genes encoding mitochondrial proteins. Moreover, mitochondrial genes exhibit a higher rate of mutation due to the generation of Reactive oxygen species (ROS) during oxidative phosphorylation operating in their vicinity. Among the different complexes of Electron transport chain (ETC), NADH: Ubiquinone oxidoreductase (Mitochondrial complex I) is the most important. This multimeric enzyme, composed of 44 subunits, is encoded by both nuclear and mitochondrial genes. It often exhibits mutations resulting in development of various neurological diseases. The most prominent diseases include leigh syndrome (LS), leber hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy associated with ragged-red fibers (MERRF), idiopathic Parkinson's disease (PD) and, Alzheimer’s disease (AD). Preliminary data suggest that mitochondrial complex I subunit genes mutated are frequently of nuclear origin; however, most of the mtDNA gene encoding subunits are also primarily involved. In this review, we have discussed the genetic origins of neurological disorders involving mitochondrial complex I and signified recent approaches to unravel the diagnostic and therapeutic potentials and their management. [Display omitted] •Comprehensive update on the mitochondrial complex-I associated neurological disorders.•Mutational outlook of the rare neurological disorders with their clinical significance.•Therapeutic advancements and clinical trials in the management of primary mitochondrial disorders.