Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes (Cell, 2007, 131:476-491)

報告日期: 2008/05/13
報告時間: 16:05/16:55
報告學生: 鄭蕙芬
講評老師: 施桂月


Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes

Cell (2007) 131: 476-491


Speaker: Huei-Fen Jheng

Commentator: Dr. Guey-Yueh Shi

Date: 05/13/2008

Place: 602


Oxidative phosphorylation (OxPhos) is one of major energy conversional functions in mitochondria. The deficiency of OxPhos causes metabolic defects in ATP synthesis, fatty acid oxidation and aerobic glucose metabolism, leading to a variety of disorders. Studies have showed the correlation between defected OxPhos and insulin resistance, implicating impaired OxPhos as an underlying genetic element for development of diabetes and obesity. However, the consistency of this correlation has been speculated. Because reactive oxygen species (ROS) accumulation result from OxPhos deficiency could also lead to insulin resistance. To study the causative nature of the primary OxPhos deficiencies in insulin resistance, the authors generated muscle- and liver-specific apoptosis-inducing factor (AIF) ablation mice with three criteria: (1) modest; (2) generalized; and (3) ROS-dissociable OxPhos deficit. These tissue-specific AIF knockout mice all exhibited defective mitochondrial oxidative phosphorylation with enhanced respiratory control and altered substrate access. The tissue-specific AIF knockout mice also showed increased glucose tolerance, reduced fat mass and increased insulin sensitivity in normal chow and high-fat feeding. The tendency of anaerobic glucose metabolism in OxPhos-reduced mice caused the compensatory increase in fuel utilization for energy demand. AIF hypomorph harlequin mice (Hq mice) which showed ubiquitous OxPhos defect also had improved glucose metabolism similar with tissue-specific AIF knockout mice. In conclusion, these results indicate primary OxPhos defects do not cause insulin resistance but improve glucose turnover, and implicated AIF as an important regulator of obesity and diabetes.



1. Joza. et al., (2005) Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy. Mol. Cell. Biol. 25, 10261–10272.

2. Lowell and Shulman (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307, 384–387.

3. Porter and Urbano (2006) Does apoptosis-inducing factor (AIF) have both life and death functions in cells? BioEssays 28, 834-843