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 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.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. civitaae@pbrc.edu <civitaae@pbrc.edu>
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Civitarese
authors.forename: Paul S
authors.initials: PS
authors.lastname: MacLean
authors.forename: Stacy
authors.initials: S
authors.lastname: Carling
authors.forename: Lyndal
authors.initials: L
authors.lastname: Kerr-Bayles
authors.forename: Ryan P
authors.initials: RP
authors.lastname: McMillan
authors.forename: Anson
authors.initials: A
authors.lastname: Pierce
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Becker
authors.forename: Cedric
authors.initials: C
authors.lastname: Moro
authors.forename: Jean
authors.initials: J
authors.lastname: Finlayson
authors.forename: Natalie
authors.initials: N
authors.lastname: Lefort
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Lawrence
authors.initials: L
authors.lastname: Mandarino
authors.forename: William
authors.initials: W
authors.lastname: Cefalu
authors.forename: Ken
authors.initials: K
authors.lastname: Walder
authors.forename: Greg R
authors.initials: GR
authors.lastname: Collier
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hulver
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D045726:Metalloproteases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D007328:Insulin; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D014157:Transcription Factors; D006003:Glycogen; D045726:Metalloproteases; C485223:PARL protein, human; C512710:PARL protein, mouse
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