Maria Rosa Ciriolo
University of Rome “Tor Vergataâ€, Rome
Italy
Title: FoxO1 redistribution from mitochondria to nucleus drives browning of white adipose tissue upon nutrient stress
Biography
Biography: Maria Rosa Ciriolo
Abstract
Adipocytes readapt their metabolism to external stimuli restraining stress conditions. Mitochondria represent the central core of these responses. Here we show that nutrient starvation in white and beige adipocytes causes generation of mitochondrial ROS (mtROS), mitonuclear protein imbalance as well as the induction of brown-related genes. A newly identified mitochondrial phosphorylated form of FoxO1 (mtFoxO1) drives this metabolic adaptation via an mtROS-dependent fashion. mtROS induces mitochondrial phosphatase PTPMT1, leading to mtFoxO1 dephosphorylation and nuclear accumulation. In nuclei mitochondrial-derived FoxO1 specifically induces the expression of SOD2, UCP1 and other marks of browning including mitochondrial fission. By forcing FoxO1 into mitochondria or down-regulating UCP1, we observed an enhanced mitochondrial stress, implying that adipocyte browning is an adaptive response to nutrient starvation. Collectively, our results highlight that mitonuclear shuttling of FoxO1 has a central role in the browning program and suggest the manipulation of its mitochondrial distribution as an attractive strategy to improve the metabolic function of adipose tissue.