PGC-1alpha over-expression promotes recovery from mitochondrial dysfunction and cell injury.
Cell death from mitochondrial dysfunction and compromised bioenergetics is common after ischemia-reperfusion injury and toxicant exposure. Thus, promoting mitochondrial biogenesis is therapeutically attractive for sustaining oxidative phosphorylation and maintaining ATP-dependent cellular functions. Here, we evaluated increased mitochondrial biogenesis prior to or after oxidant exposure in primary cultures of renal proximal tubular cells (RPTC). Over-expression of the mitochondrial biogenesis regulator PPAR-gamma cofactor-1 alpha (PGC-1alpha) in control RTPC increased basal and uncoupled cellular respiration, ATP, and mitochondria. Increasing mitochondrial number/function prior to oxidant exposure did not preserve mitochondrial function, but potentiated dysfunction and cell death. However, increased mitochondrial biogenesis after oxidant injury accelerated recovery of mitochondrial function. In oxidant treated RPTC, mitochondrial protein expression was reduced by 50%. Also, ATP and cellular respiration decreased 48 h after oxidant exposure, whereas mitochondrial function in injured RPTC over-expressing PGC-1alpha returned to control values. Thus, up-regulation of mitochondrial biogenesis after oxidant exposure accelerates recovery of mitochondrial and cellular functions.
Rasbach
Kyle A
KA
Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun St. POB 250140, Charleston, SC 29425, USA.
Schnellmann
Rick G
RG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D019069:Cell Respiration; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000633:toxicity; D017136:Ion Transport; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D047495:PPAR gamma; D000255:Adenosine Triphosphate; D012964:Sodium; D006861:Hydrogen Peroxide