| First Author | Nowak G | Year | 2020 |
| Journal | FEBS J | Volume | 287 |
| Issue | 9 | Pages | 1830-1849 |
| PubMed ID | 31659858 | Mgi Jnum | J:309051 |
| Mgi Id | MGI:6755259 | Doi | 10.1111/febs.15110 |
| Citation | Nowak G, et al. (2020) Protein kinase Calpha mediates recovery of renal and mitochondrial functions following acute injury. FEBS J 287(9):1830-1849 |
| abstractText | Previously, we have shown that active protein kinase Calpha (PKCalpha) 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 PKCalpha 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 Fo F1 -ATPase decreased after ischemia and recovered in WT mice. Reperfusion after ischemia was accompanied by translocation of active PKCalpha to mitochondria. PKCalpha deletion reduced mitochondrial respiration and activities of respiratory complex I and Fo F1 -ATPase in noninjured kidneys, indicating that PKCalpha is essential in developing fully functional renal mitochondria. These changes in PKCalpha-deficient mice were accompanied by lower levels of complex I subunits (NDUFA9 and NDUFS3) and the gamma-subunit of Fo F1 -ATPase. Also, lack of PKCalpha exacerbated ischemia-induced decreases in respiration, complex I and Fo F1 -ATPase activities, and blocked their recovery after injury, indicating a crucial role of PKCalpha in promoting mitochondrial recovery after AKI. Further, PKCalpha 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 PKCalpha in regulating levels of mitochondrial sirtuins and acetylation and succinylation of key mitochondrial proteins. We conclude that PKCalpha 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. |
