Protein Kinase C-α Interaction with F0F1-ATPase Promotes F0F1-ATPase Activity and Reduces Energy Deficits in Injured Renal Cells

Nowak, Grażyna; Bakajsova, Diana

doi:10.1074/jbc.m114.588244

Cited by 12 publications

(17 citation statements)

References 40 publications

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“…Previously, we have demonstrated that PKCα interacts with F 0 F 1 ‐ATPase in renal proximal tubular cells, increases phosphorylation of α‐, β‐, and γ‐ subunits of F 0 F 1 ‐ATPase, prevents their degradation, and thus promotes mitochondrial function and ATP content in these cells after injury . Our present data support a novel observation that PKCα regulates the acetylation and succinylation of lysine residues of proteins in renal cortical mitochondria.…”

Section: Resultssupporting

confidence: 88%

“…Activation of PKCα is also involved in chemically induced injury in LLCPK1 cells and in cultured renal proximal tubules in vitro . We have shown that oxidant injury activates PKCα and induces translocation of active PKCα to mitochondria, which promotes recovery of mitochondrial function and ATP levels in injured renal proximal tubular cells in vitro . Further, we have shown that the F 1 domain of F o F 1 ‐ATPase (ATP synthase) is a mitochondrial target of PKCα in oxidant‐injured renal proximal tubules in vitro .…”

Section: Introductionmentioning

confidence: 88%

“…We have shown that oxidant injury activates PKCα and induces translocation of active PKCα to mitochondria, which promotes recovery of mitochondrial function and ATP levels in injured renal proximal tubular cells in vitro . Further, we have shown that the F 1 domain of F o F 1 ‐ATPase (ATP synthase) is a mitochondrial target of PKCα in oxidant‐injured renal proximal tubules in vitro . However, the role of PKCα in mitochondrial dysfunction, kidney tissue injury, and decreases in renal functions after AKI in vivo is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Protein kinase Cα mediates recovery of renal and mitochondrial functions following acute injury

Nowak

Megyesi

2019

The FEBS Journal

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Previously, we have shown that active protein kinase Ca (PKCa) 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 PKCa 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 -ATPase decreased after ischemia and recovered in WT mice. Reperfusion after ischemia was accompanied by translocation of active PKCa to mitochondria. PKCa deletion reduced mitochondrial respiration and activities of respiratory complex I and F o F 1 -ATPase in noninjured kidneys, indicating that PKCa is essential in developing fully functional renal mitochondria. These changes in PKCadeficient mice were accompanied by lower levels of complex I subunits (NDUFA9 and NDUFS3) and the c-subunit of F o F 1 -ATPase. Also, lack of PKCa exacerbated ischemia-induced decreases in respiration, complex I and F o F 1 -ATPase activities, and blocked their recovery after injury, indicating a crucial role of PKCa in promoting mitochondrial recovery after AKI. Further, PKCa 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 PKCa in regulating levels of mitochondrial sirtuins and acetylation and succinylation of key mitochondrial proteins. We conclude that PKCa 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. EnzymesProtein kinase C: EC 2.

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Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Protein kinase Cα mediates recovery of renal and mitochondrial functions following acute injury

Nowak

Megyesi

2019

The FEBS Journal

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“…PKC signaling also regulates the mitoK ATP channel (40), inhibits the opening of the permeability transition pore (41), and regulates mitochondrial-mediated apoptosis upon B-cell lymphoma 2 (Bcl-2)-associated death promoter (42) and Bcl2 phosphorylation (43). PKCa-dependent activation of complex I, IV and, ATP synthase promotes recovery of mitochondrial function and cell survival in injured renal cells (44).…”

mentioning

confidence: 99%

Coordinated activation of mitochondrial respiration and exocytosis mediated by PKC signaling in pancreatic β cells

Santo‐Domingo¹,

Chareyron²,

Dayon³

et al. 2016

FASEB j.

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Mitochondria play a central role in pancreatic β-cell nutrient sensing by coupling their metabolism to plasma membrane excitability and insulin granule exocytosis. Whether non-nutrient secretagogues stimulate mitochondria as part of the molecular mechanism to promote insulin secretion is not known. Here, we show that PKC signaling, which is employed by many non-nutrient secretagogues, augments mitochondrial respiration in INS-1E (rat insulinoma cell line clone 1E) and human pancreatic β cells. The phorbol ester, phorbol 12-myristate 13-acetate, accelerates mitochondrial respiration at both resting and stimulatory glucose concentrations. A range of inhibitors of novel PKC isoforms prevent phorbol ester-induced respiration. Respiratory response was blocked by oligomycin that demonstrated PKC-dependent acceleration of mitochondrial ATP synthesis. Enhanced respiration was observed even when glycolysis was bypassed or fatty acid transport was blocked, which suggested that PKC regulates mitochondrial processes rather than upstream catabolic fluxes. A phosphoproteome study of phorbol ester-stimulated INS-1E cells maintained under resting (2.5 mM) glucose revealed a large number of phosphorylation sites that were altered during short-term activation of PKC signaling. The data set was enriched for proteins that are involved in gene expression, cytoskeleton remodeling, secretory vesicle transport, and exocytosis. Interactome analysis identified PKC, C-Raf, and ERK1/2 as the central phosphointeraction cluster. Prevention of ERK1/2 signaling by using a MEK1 inhibitor caused a marked decreased in phorbol 12-myristate 13-acetate-induced mitochondrial respiration. ERK1/2 signaling module therefore links PKC activation to downstream mitochondrial activation. We conclude that non-nutrient secretagogues act, in part, PKC and downstream ERK1/2 signaling to stimulate mitochondrial energy production to compensate for energy expenditure that is linked to β-cell activation.-Santo-Domingo, J., Chareyron, I., Dayon, L., Galindo, A. N., Cominetti, O., Giménez, M. P. G., De Marchi, U., Canto, C., Kussmann, M., Wiederkehr, A. Coordinated activation of mitochondrial respiration and exocytosis mediated by PKC signaling in pancreatic β cells.

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“…Phosphorylation of the mitochondrial OXPHOS complexes is mediated by protein kinases. At least some of the kinases are allosterically regulated by cyclic-AMP, which involves, among other ones, the action of a novel, mitochondrial-specific soluble adenylate cyclase (De Rasmo et al, 2015;Nowak & Bakajsova, 2015;Valsecchi, Konrad, & Manfredi, 2014;Valsecchi et al, 2013). As mentioned, the role of (reversible) phosphorylation of bacterial respiratory complexes is not understood, no more than possible signalling pathways either.…”

Section: Protein Phosphorylationmentioning

confidence: 99%

Bacterial Electron Transfer Chains Primed by Proteomics

Wessels¹,

Almeida²,

Kartal³

et al. 2016

Advances in Bacterial Electron Transport Systems and Their Regulation

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Electron transport phosphorylation is the central mechanism for most prokaryotic species to harvest energy released in the respiration of their substrates as ATP. Microorganisms have evolved incredible variations on this principle, most of these we perhaps do not know, considering that only a fraction of the microbial richness is known. Besides these variations, microbial species may show substantial versatility in using respiratory systems. In connection herewith, regulatory mechanisms control the expression of these respiratory enzyme systems and their assembly at the translational and posttranslational levels, to optimally accommodate changes in the supply of their energy substrates. Here, we present an overview of methods and techniques from the field of proteomics to explore bacterial electron transfer chains and their regulation at levels ranging from the whole organism down to the Ångstrom scales of protein structures. From the survey of the literature on this subject, it is concluded that proteomics, indeed, has substantially contributed to our comprehending of bacterial respiratory mechanisms, often in elegant combinations with genetic and biochemical approaches. However, we also note that advanced proteomics offers a wealth of opportunities, which have not been exploited at all, or at best underexploited in hypothesis-driving and hypothesis-driven research on bacterial bioenergetics. Examples obtained from the related area of mitochondrial oxidative phosphorylation research, where the application of advanced proteomics is more common, may illustrate these opportunities.

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Protein Kinase C-α Interaction with F0F1-ATPase Promotes F0F1-ATPase Activity and Reduces Energy Deficits in Injured Renal Cells

Cited by 12 publications

References 40 publications

Protein kinase Cα mediates recovery of renal and mitochondrial functions following acute injury

Protein kinase Cα mediates recovery of renal and mitochondrial functions following acute injury

Coordinated activation of mitochondrial respiration and exocytosis mediated by PKC signaling in pancreatic β cells

Bacterial Electron Transfer Chains Primed by Proteomics

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