Regulation of Skeletal Muscle Oxidative Capacity and Insulin Signaling by the Mitochondria! Rhomboid Protease PARL

被引：75

作者：

Civitarese, Anthony E. ^{[1
,2
,9
]}

MacLean, Paul S. ^{[3
]}

Carling, Stacy ^{[1
]}

Kerr-Bayles, Lyndal ^{[4
]}

McMillan, Ryan P. ^{[6
]}

Pierce, Anson ^{[7
]}

Becker, Thomas C. ^{[8
]}

Moro, Cedric ^{[1
]}

Finlayson, Jean ^{[2
]}

Lefort, Natalie ^{[2
]}

Newgard, Christopher B. ^{[8
]}

Mandarino, Lawrence ^{[2
,9
]}

Cefalu, William ^{[1
]}

Walder, Ken

Collier, Greg R. ^{[5
]}

Hulver, Matthew W. ^{[6
]}

Smith, Steven R. ^{[1
]}

Ravussin, Eric ^{[1
]}

机构：

[1] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA

[2] Arizona State Univ, Tempe, AZ 85287 USA

[3] Univ Colorado, Denver, CO 80045 USA

[4] Deakin Univ, Geelong, Vic 3220, Australia

[5] ChemGenex Pharmaceut, Geelong, Vic 3220, Australia

[6] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA

[7] Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA

[8] Duke Univ, Durham, NC 27708 USA

[9] Mayo Clin, Dept Med, Scottsdale, AZ 85259 USA

来源：

CELL METABOLISM | 2010年 / 11卷 / 05期

关键词：

TYPE-2 DIABETIC PARENTS; FATTY-ACID OXIDATION; IN-VIVO; ENERGY-METABOLISM; RECEPTOR SUBSTRATE-1; LIPID CONCENTRATIONS; TRANSMITTING CABLES; HEPATIC STEATOSIS; RESISTANCE; OPA1;

D O I：

10.1016/j.cmet.2010.04.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Type 2 diabetes mellitus (T2DM) and aging are characterized by insulin resistance and impaired mitochondria! 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 PGC1 alpha 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 PAR L expression may contribute to the mitochondrial abnormalities seen in aging and T2DM.

引用

页码：412 / 426

页数：15

共 88 条

[71] PGC-1β controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis [J].