Oxidants and Ca+2 induce PGC-1α degradation through calpain

Kyle A. Rasbach, Peter T. Green, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Peroxisome proliferator activator receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator known to mediate mitochondrial biogenesis. Whereas PGC-1α transcription is regulated by a variety of signaling cascades, the mechanisms of PGC-1α degradation have received less investigation. Thus, we investigated the mechanisms responsible for PGC-1α degradation in renal proximal tubular cells (RPTC). Amino acid sequence analysis of the PGC-1α protein revealed three PEST sequence-rich regions, predictive of proteolysis by calpains and/or the proteasome. Under basal conditions, treatment with the protein synthesis inhibitor cycloheximide resulted in rapid degradation of PGC-1α (t1/2 = 38 min), which was blocked by the proteasome inhibitor epoxomicin, but not the calpain inhibitor calpeptin. Oxidant exposure resulted in the degradation of both endogenous and adenovirally over-expressed PGC-1α, which was inhibited by calpeptin but not epoxomicin. Thapsigargin-induced release of ER Ca2+ also stimulated calpain-dependent, epoxomicin-independent degradation of PGC-1α. Finally, Ca2+ addition to lysates of RPTC over-expressing PGC-1α resulted in calpeptin-sensitive, epoxomicin-insensitive degradation of PGC-1α. In summary, we suggest two distinct mechanisms regulate PGC-1α: basal PGC-1α turnover by proteasome degradation and oxidant- and Ca2+-mediated PGC-1α degradation through calpain.

Original languageEnglish (US)
Pages (from-to)130-135
Number of pages6
JournalArchives of Biochemistry and Biophysics
Issue number2
StatePublished - Oct 15 2008
Externally publishedYes


  • Calcium
  • Calpain
  • Kidney
  • Mitochondrial biogenesis
  • Oxidant
  • PGC-1α
  • Proteasome

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


Dive into the research topics of 'Oxidants and Ca+2 induce PGC-1α degradation through calpain'. Together they form a unique fingerprint.

Cite this