ABSTRACT
Mitochondrial complex I (NADH: Ubiquinone Oxidoreductase; CI) (~45 subunits, Mol. Wt= 1 MDa) is important in electron transport chain (ETC), oxidative phosphorylation (OXPHOS) and ATP production in eukaryotes. CI connects electron transfer with proton translocation and forms higher-order supercomplexes with other ETC complexes. CI has received increased attention by scientists and clinicians in recent period due to its direct role in human diseases. Although mutations in CI subunits and altered expression could potentially lower CI activity in many diseases, post-translational modifications (PTMs) have emerged as an important mechanism contributing to altered CI activity. These PTMs include oxidative modifications such as cysteine modifications, tyrosine nitration, tryptophan oxidation, carbonylation, and non-oxidative modifications such as phosphorylation, methylation and acetylation. Many of these modifications are transient making comprehensive analysis under varied physiological paradigms difficult. Study of these PTMs and their contribution to the structure-function relationship of CI are incomplete in pathological conditions. This chapter intends to highlight the role of PTMs in CI structure and function with implications for pathobiology of CNS diseases.
