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

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 Murphy, Bruce S Kristal, Steven P Gygi & Bruce M Spiegelman
Brown adipose tissue (BAT) mitochondria exhibit high oxidative capacity and abundant expression of both electron transport chain components and uncoupling protein 1 (UCP1). UCP1 dissipates the mitochondrial proton motive force (Δp) generated by the respiratory chain and increases thermogenesis. Here we find that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT. Moreover, global proteomic analysis reveals that this cascade induced by UCP1 deletion...

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