Research: GUO and COLLEAGUES,

Listed in Issue 243

Abstract

GUO and COLLEAGUES,  (1)Department of Pharmacology studied in diabetic mice liver mitochondrial dysfunction pathways.

Background

Insulin resistance plays a major role in the development of type 2 diabetes and obesity and affects a number of biological processes such as mitochondrial biogenesis. Though mitochondrial dysfunction has been linked to the development of insulin resistance and pathogenesis of type 2 diabetes, the precise mechanism linking the two is not well understood.

Methodology

The authors used high fat diet (HFD)-induced obesity dependent diabetes mouse models to gain insight into the potential pathways altered with metabolic disease, and carried out quantitative proteomic analysis of liver mitochondria.

Results

As previously reported, proteins involved in fatty acid oxidation, branched chain amino acid degradation, tricarboxylic acid cycle, and oxidative phosphorylation were uniformly up-regulated in the liver of HFD fed mice compared with that of normal diet. Further, our studies revealed that retinol metabolism is distinctly down-regulated and the mitochondrial structural proteins-components of mitochondrial inter-membrane space bridging (MIB) complex (Mitofilin, Sam50, and ChChd3), and Tim proteins-essential for protein import, are significantly up-regulated in HFD fed mice. Structural and functional studies on HFD and normal diet liver mitochondria revealed remodelling of HFD mitochondria to a more condensed form with increased respiratory capacity and higher ATP levels compared with normal diet mitochondria.

Conclusion

Thus, it is likely that the structural remodelling is essential to accommodate the increased protein content in presence of HFD: the mechanism could be through the MIB complex promoting contact site and crista junction formation and in turn facilitating the lipid and protein uptake.

References

Guo Y(1), Darshi M, Ma Y, Perkins GA, Shen Z, Haushalter KJ, Saito R, Chen A, Lee YS, Patel HH, Briggs SP, Ellisman MH, Olefsky JM, Taylor SS. Quantitative proteomic and functional analysis of liver mitochondria from high fat diet (HFD) diabetic mice. Mol Cell Proteomics. 12(12):3744-58. doi: 10.1074/mcp.M113.027441. Dec 2013. Epub Sep 12 2013.

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