PGC-1α over-expression promotes recovery from mitochondrial dysfunction and cell injury

Kyle A. Rasbach, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)734-739
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume355
Issue number3
DOIs
StatePublished - Apr 13 2007
Externally publishedYes

Keywords

  • Cell death
  • Ischemia-reperfusion
  • Mitochondrial biogenesis
  • Mitochondrial function
  • Oxidant
  • PGC-1α
  • Renal cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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