PGRMC2 is an Intracellular Heme Chaperone Critical for Adipocyte Function

We describe a role for the poorly annotated protein PGRMC2 in retrograde transport of heme from mitochondria to the nucleus. In absence of PGRMC2, less signaling heme reaches the nucleus, with a consequent alteration of heme-sensitive transcriptional programs that ultimately engenders severe mitochondrial dysfunction in brown adipocytes. These mitochondrial defects compromise, not only the primary function of BAT, to activate thermogenesis and preserve body temperature, but also its contribution to maintain systemic glucose and lipid homeostasis. PolyA+ RNAseq profilling of Brown Adipose Tissue (BAT) isolated from wild-type and PGRMC2 adipose tissue knockout mice housed at 30°C