walder-regulationof-2010.pdf (1.75 MB)
Regulation of skeletal muscle oxidative capacity and insulin signaling by the Mitochondrial Rhomboid Protease PARL
journal contribution
posted on 2010-05-05, 00:00 authored by Anthony Civitarese, P MacLean, S Carling, L Kerr-Bayles, R McMillan, A Pierce, T Becker, C Moro, J Finlayson, N Lefort, C Newgard, L Mandarino, W Cefalu, Ken WalderKen Walder, Gregory Collier, M Hulver, S Smith, E RavussinType 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.
History
Journal
Cell metabolismVolume
11Issue
5Pagination
412 - 426Publisher
Cell PressLocation
Cambridge, Mass.Publisher DOI
ISSN
1550-4131eISSN
1932-7420Language
engPublication classification
C1 Refereed article in a scholarly journal; C Journal articleCopyright notice
2010, ElsevierUsage metrics
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