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Protein kinase Cα mediates recovery of renal and mitochondrial functions following acute injury
Author(s) -
Nowak Grazyna,
Megyesi Judit
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15110
Subject(s) - mitochondrion , protein kinase c , ischemia , kidney , biology , renal ischemia , succinylation , biochemistry , microbiology and biotechnology , reperfusion injury , chemistry , medicine , acetylation , endocrinology , kinase , gene
Previously, we have shown that active protein kinase Cα ( PKC α) promotes recovery of mitochondrial function after injury in vitro [Nowak G & Bakajsova D (2012) Am J Physiol Renal Physiol 303, F515‐F526]. This study examined whether PKC α regulates recovery of mitochondrial and kidney functions after ischemia‐induced acute injury ( AKI ) in vivo . Markers of kidney injury were increased after bilateral ischemia and returned to normal levels in wild‐type ( WT ) mice. Maximum mitochondrial respiration and activities of respiratory complexes and F o F 1 ‐ ATP ase decreased after ischemia and recovered in WT mice. Reperfusion after ischemia was accompanied by translocation of active PKC α to mitochondria. PKC α deletion reduced mitochondrial respiration and activities of respiratory complex I and F o F 1 ‐ ATP ase in noninjured kidneys, indicating that PKC α is essential in developing fully functional renal mitochondria. These changes in PKC α‐deficient mice were accompanied by lower levels of complex I subunits ( NDUFA 9 and NDUFS 3) and the γ‐subunit of F o F 1 ‐ ATP ase. Also, lack of PKC α exacerbated ischemia‐induced decreases in respiration, complex I and F o F 1 ‐ ATP ase activities, and blocked their recovery after injury, indicating a crucial role of PKC α in promoting mitochondrial recovery after AKI . Further, PKC α deletion exacerbated acetylation and succinylation of key mitochondrial proteins of energy metabolism after ischemia due to decreases in deacetylase and desuccinylase (sirtuin3 and sirtuin5) levels in renal mitochondria. Thus, our data show a novel role for PKC α in regulating levels of mitochondrial sirtuins and acetylation and succinylation of key mitochondrial proteins. We conclude that PKC α deletion: (a) affects renal physiology by decreasing mitochondrial capacity for maximum respiration; (b) blocks recovery of mitochondrial functions, renal morphology, and functions after AKI ; and (c) decreases survival after AKI . Enzymes Protein kinase C: EC 2.7.11.13; NADH : ubiquinone reductase (H + ‐translocating; complex I): EC 7.1.1.2; FoF1‐ATPase (H + ‐transporting two‐sector ATPase): EC 7.1.2.2; Succinate : ubiquinone oxidoreductase (complex II): EC 1.3.5.1; Ubiquinol : cytochrome‐ c reductase (complex III): EC 7.1.1.8; Cytochrome c oxidase (complex IV): EC 1.9.3.1; NAD‐dependent protein deacetylase sirtuin‐3, mitochondrial: EC 2.3.1.286; NAD‐dependent protein deacetylase sirtuin‐5, mitochondrial: EC 3.5.1.‐; Proteinase K (peptidase K): EC 3.4.21.64.