TY - JOUR
T1 - PGC-1α over-expression promotes recovery from mitochondrial dysfunction and cell injury
AU - Rasbach, Kyle A.
AU - Schnellmann, Rick G.
N1 - Funding Information:
We thank Dr. Bruce Spiegelman (Harvard Medical School) for the generous gift of the adenoviral constructs used to express PGC-1α and GFP in these experiments. Work was performed with funding from National Institutes of Health Training Grant T32 HL007260.
PY - 2007/4/13
Y1 - 2007/4/13
N2 - 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-γ cofactor-1 alpha (PGC-1α) 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-1α returned to control values. Thus, up-regulation of mitochondrial biogenesis after oxidant exposure accelerates recovery of mitochondrial and cellular functions.
AB - 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-γ cofactor-1 alpha (PGC-1α) 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-1α returned to control values. Thus, up-regulation of mitochondrial biogenesis after oxidant exposure accelerates recovery of mitochondrial and cellular functions.
KW - Cell death
KW - Ischemia-reperfusion
KW - Mitochondrial biogenesis
KW - Mitochondrial function
KW - Oxidant
KW - PGC-1α
KW - Renal cells
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U2 - 10.1016/j.bbrc.2007.02.023
DO - 10.1016/j.bbrc.2007.02.023
M3 - Article
C2 - 17307137
AN - SCOPUS:33847253895
SN - 0006-291X
VL - 355
SP - 734
EP - 739
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -