UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction

Authors: Lawrence Kazak, Edward T. Chouchani, Irina G. Stavrovskaya, Gina Z. Lu, Mark P. Jedrychowski, Daniel F. Egan, Manju Kumari, Xingxing Kong, Brian K. Erickson, John Szpyt, Evan D. Rosen, Michael P. Murphy, Bruce S. Kristal, Steven P. Gygi, Bruce M. Spiegelman - Proceedings of the National Academy of Sciences, PNAS 2017 cited by 180

Significance We describe a physiological role for uncoupling protein 1 (UCP1) in the regulation of reactive oxygen species. Notably, the molecular differences between brown fat mitochondria from wild-type and UCP1 knockout (UCP1-KO) mice extend substantially beyond the deletion of UCP1 itself. Thus, caution must be taken when attributing a brown fat phenotype solely to UCP1 deletion when these animals are used. Given the wide utilization of the UCP1-KO mouse model, these data are of critical importance for the scientific communities studying obesity, thermogenesis and energy metabolism, and mitochondrial biology.