Journal article
Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice
JA Wali, S Galic, CYR Tan, EN Gurzov, AE Frazier, T Connor, J Ge, EG Pappas, D Stroud, LC Varanasi, C Selck, MT Ryan, DR Thorburn, BE Kemp, B Krishnamurthy, TWH Kay, SL McGee, HE Thomas
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2018
DOI: 10.1038/cdd.2017.168
Abstract
BCL-2 proteins are known to engage each other to determine the fate of a cell after a death stimulus. However, their evolutionary conservation and the many other reported binding partners suggest an additional function not directly linked to apoptosis regulation. To identify such a function, we studied mice lacking the BH3-only protein BIM. BIM-/- cells had a higher mitochondrial oxygen consumption rate that was associated with higher mitochondrial complex IV activity. The consequences of increased oxygen consumption in BIM-/- mice were significantly lower body weights, reduced adiposity and lower hepatic lipid content. Consistent with reduced adiposity, BIM-/- mice had lower fasting blood g..
View full abstractGrants
Funding Acknowledgements
We thank Lorraine Elkerbout, Stacey Fynch, William Stanley, Jasmine McLeod, Lara Yachou-Wos, Sam Thorburn, Eva Orlowski (all St Vincent's Institute), Adrienne Laskowski (Murdoch Childrens Research Institute), Philippe Bouillet, Andreas Strasser, Lorraine O'Reilly, Marco Herold, Margs Brennan, David Huang, David Segal (The Walter and Eliza Hall Institute), Sara Ellis, Jill Danne and Chad Johnson (Peter MacCallum Cancer Centre), Greg Steinberg (McMaster University, Canada) and Sof Andrikopoulos (University of Melbourne) for experimental advice, technical assistance, reagents and critical reading of the manuscript. This work was funded by a National Health and Medical Research Council of Australia (NHMRC) Project grant, a NHMRC and Juvenile Diabetes Research Foundation joint special programme grant, and fellowships from the NHMRC. This work received support from the Operational Infrastructure Support Scheme of the Government of Victoria.