Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL.

Journal Article (Journal Article)

Type 2 diabetes mellitus (T2DM) and aging are characterized by insulin resistance and impaired mitochondrial energetics. In lower organisms, remodeling by the protease pcp1 (PARL ortholog) maintains the function and lifecycle of mitochondria. We examined whether variation in PARL protein content is associated with mitochondrial abnormalities and insulin resistance. PARL mRNA and mitochondrial mass were both reduced in elderly subjects and in subjects with T2DM. Muscle knockdown of PARL in mice resulted in malformed mitochondrial cristae, lower mitochondrial content, decreased PGC1alpha protein levels, and impaired insulin signaling. Suppression of PARL protein in healthy myotubes lowered mitochondrial mass and insulin-stimulated glycogen synthesis and increased reactive oxygen species production. We propose that lower PARL expression may contribute to the mitochondrial abnormalities seen in aging and T2DM.

Full Text

Duke Authors

Cited Authors

  • Civitarese, AE; MacLean, PS; Carling, S; Kerr-Bayles, L; McMillan, RP; Pierce, A; Becker, TC; Moro, C; Finlayson, J; Lefort, N; Newgard, CB; Mandarino, L; Cefalu, W; Walder, K; Collier, GR; Hulver, MW; Smith, SR; Ravussin, E

Published Date

  • May 5, 2010

Published In

Volume / Issue

  • 11 / 5

Start / End Page

  • 412 - 426

PubMed ID

  • 20444421

Pubmed Central ID

  • PMC3835349

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2010.04.004


  • eng

Conference Location

  • United States