@article{61e30b72d7834a87a829ab1231fa3667,
title = "Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL",
abstract = "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 PGC1α 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.",
author = "Civitarese, {Anthony E.} and MacLean, {Paul S.} and Stacy Carling and Lyndal Kerr-Bayles and McMillan, {Ryan P.} and Anson Pierce and Becker, {Thomas C.} and Cedric Moro and Jean Finlayson and Natalie Lefort and Newgard, {Christopher B.} and Lawrence Mandarino and William Cefalu and Ken Walder and Collier, {Greg R.} and Hulver, {Matthew W.} and Smith, {Steven R.} and Eric Ravussin",
note = "Funding Information: The mCK-CAR mice were made available by Dr. Josephine Nalbantoglu and Dr. Paul Holland at McGill University. We appreciate the technical assistance of Ginger Johnson, Brooke Fleming-Elder, Jeremy Ravussin, Phirom Saly, and Tianna Stubblefield. The authors would also like to thank Dr. Clifton Bogardus and the NIDDK for their generosity in supplying muscle samples from the Pima Indians. This work was supported, in part, by RO1 AG20478 (E.R.), P30 DK072476 (E.R.), DK67403 (P.S.M.), RO1 DK 078765 (M.W.H.), Pennington Institutional grant from the Health & Performance Enhancement Division (A.E.C.), and the John S. McIlhenny Foundation (A.E.C.). ",
year = "2010",
month = may,
day = "5",
doi = "10.1016/j.cmet.2010.04.004",
language = "English (US)",
volume = "11",
pages = "412--426",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}