Mapping the protein phosphorylation sites in human mitochondrial complex I (NADH: Ubiquinone oxidoreductase): A bioinformatics study with implications for brain aging and neurodegeneration

The Role of Reversible Protein Phosphorylation in Regulation of the Mitochondrial Electron Transport System During Hypoxia and Reoxygenation Stress in Marine Bivalves

“…While a comparable bioinformatics map could not be found for mammals, the important role of PKA-dependent phosphorylation in regulation of the Complex IV activity has been shown experimentally in humans and other mammals (Helling et al, 2012;Castellanos and Lanning, 2019). High number of the candidate phosphorylation sites in the Complexes I and IV of marine bivalves indicates a considerable potential for this PTM mechanism to regulate ETS activity, even if not all the putative phosphorylation sites undergo reversible phosphorylation in vivo (Chen et al, 2004;Papa et al, 2012;Gowthami et al, 2019). This hypothesis is supported by the results of the experimental manipulation of the enzyme phosphorylation state showing that mitochondrial Complexes I and IV of marine bivalves are sensitive to the regulation by reversible protein phosphorylation.…”

“…The number of the predicted phosphorylation sites depended on the overall size of the respective subunit, with an average of one phosphorylation site for each 3-5 amino acids. The most frequent phosphorylation sites on the bivalve Complex I mitochondrial subunits corresponded to the recognition sites for the protein kinase A (99 sites) and protein kinase C (121 sites), similar to the human Complex I (Gowthami et al, 2019). The putative PKA and PKC phosphorylation sites were also highly represented (27 and 70 sites, respectively) on the Complex IV subunits of the studied marine bivalves.…”

“…Studies in mammalian models demonstrated an important role of post-translational modification (PTM) of ETS proteins, particularly the Complexes I and IV, in regulating the responses to H/R stress including modulation of the ETS activity, protein-protein and protein-lipid interactions, and ROS production (Hüttemann et al, 2012;Dudek, 2017;Gowthami et al, 2019;Kalpage et al, 2019;Mathers and Staples, 2019). Among different types of PTMs (such as phosphorylation, acetylation, succinylation, or SUMOylation), the reversible protein phosphorylation by protein kinases plays an important and not yet fully deciphered role in regulating the mitochondrial metabolism in different physiological and stress states (Stram and Payne, 2016).…”

Genome-Wide Identification and Characterization of Long Noncoding RNAs of Brown to White Adipose Tissue Transformation in Goats

“…In addition, there are many target genes encoding the subunits of NADH dehydrogenase, which is the center of complex I, embedded in the inner mitochondrial membrane. The transferring of electrons from nicotinamide adenine dinucleotide (NADH) to coenzyme Q (CoQ) is regulated by NADH dehydrogenase [69,70]. Interestingly, UCP1 is the primary marker of BAT and plays an important role in ATP synthesis and uncouples respiratory chain activity in BAT [3].…”

Metabolic adaptations of neurons to physiological oxygen concentrations

“…Activity and assembly regulation of CI is mediated by phosphorylation of some CI subunits by specific kinases (Papa et al, 2002;. There are a total of 1496 residues that would be phosphorylated in human CI, Phosphorylation is higher among core subunits and active domains of the complex, among which NDUFS1 displayed significantly higher number as well as percent phospho sites and NDUFA5 contains the least number of potentially phosphorylated residues (Gowthami et al, 2018). Thus, phosphorylation of serine-250 in complex I subunit NdufA10 was needed for ubiquinone reduction by complex I (Morais et al, 2014).…”