| Title | Cardiolipin Remodeling by ALCAT1 Links Oxidative Stress and Mitochondrial Dysfunction to Obesity |
| Authors | Li, Jia Romestaing, Caroline Han, Xianlin Li, Yuan Hao, Xinbao Wu, Yinyuan Sun, Chao Liu, Xiaolei Jefferson, Leonard S. Xiong, Jingwei LaNoue, Kathryn F. Chang, Zhijie Lynch, Christopher J. Wang, Huayan Shi, Yuguang |
| Affiliation | Penn State Univ, Dept Cellular & Mol Physiol, Coll Med, Hershey, PA 17033 USA. NW A&F Univ, Shaanxi Ctr Stem Cell Engn & Technol, Yangling, Shaanxi, Peoples R China. Washington Univ, Sch Med, Div Bioorgan Chem & Mol Pharmacol, St Louis, MO 63110 USA. Tsinghua Univ, Sch Med, Sch Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. |
| Keywords | FATTY-ACID OXIDATION COMPLEX-I ACTIVITY INSULIN-RESISTANCE SKELETAL-MUSCLE DOCOSAHEXAENOIC ACID LIPID-PEROXIDATION SHOTGUN LIPIDOMICS PPAR-GAMMA ROSIGLITAZONE HEART |
| Issue Date | 2010 |
| Publisher | cell metabolism |
| Citation | CELL METABOLISM.2010,12,(2),154-165. |
| Abstract | Oxidative stress causes mitochondrial dysfunction and metabolic complications through unknown mechanisms. Cardiolipin (CL) is a key mitochondrial phospholipid required for oxidative phosphorylation. Oxidative damage to CL from pathological remodeling is implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, and other metabolic diseases. Here, we show that ALCAT1, a lyso-CL acyltransferase upregulated by oxidative stress and diet-induced obesity (DIO), catalyzes the synthesis of CL species that are highly sensitive to oxidative damage, leading to mitochondrial dysfunction, ROS production, and insulin resistance. These metabolic disorders were reminiscent of those observed in type 2 diabetes and were reversed by rosiglitazone treatment. Consequently, ALCAT1 deficiency prevented the onset of DIO and significantly improved mitochondrial complex I activity, lipid oxidation, and insulin signaling in ALCAT1(-/-) mice. Collectively, these findings identify a key role of ALCAT1 in regulating CL remodeling, mitochondrial dysfunction, and susceptibility to DIO. |
| URI | http://hdl.handle.net/20.500.11897/242559 |
| ISSN | 1550-4131 |
| DOI | 10.1016/j.cmet.2010.07.003 |
| Indexed | SCI(E) |
| Appears in Collections: | 分子医学研究所 |
