Title: Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice
Authors: Wali, JA
Galic, S
Tan, CYR
Gurzov, EN
Frazier, AE
Connor, T
Ge, JJ
Pappas, EG
Stroud, D
Varanasi, LC
Selck, C
Ryan, MT
Thorburn, DR
Kemp, BE
Krishnamurthy, B
Kay, TWH
Thomas, HE
Issue Year: 2018
Series Cell Death Differ.:
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 glucose, improved insulin sensitivity and hepatic insulin signalling. Lipid oxidation was increased in BIM-/- mice, suggesting a mechanism for their metabolic phenotype. Our data suggest a role for BIM in regulating mitochondrial bioenergetics and metabolism and support the idea that regulation of metabolism and cell death are connected.
URI: https://publications.svi.edu.au/publications/4717
Other Identifiers 10.1038/cdd.2017.168
Publication type Article