BUB1 and BUB3 regulate metabolic adaptation via macrolipophagy in Drosophila

Lipophagy, the newly discovered process of selective catabolism of lipid droplets (LDs) by autophagy, maintains lipid homeostasis and provides cellular energy under starvation, yet its underlying mechanism remains largely ambiguous. Here we show that BUB1-BUB3 complex, the key regulator involved in the whole processes of chromosome alignment and separation during mitosis, controls the fasting-induced lipid catabolism in the fat body of Drosophila during interphase. Bidirectional deviations of BUB1 or BUB3 level affect the consumption of triacylglycerol (TAG) of fat body and survival rate of adult flies under starving. Moreover, BUB1 and BUB3 work together to attenuate the lipid degradation via macrolipophagy. Thus, we uncover previously unknown physiological roles of BUB1-BUB3 complex on metabolic adaptation and lipid metabolism beyond their canonical mitotic functions, and provide new insights into the in vivo functions and molecular mechanisms of macrolipophagy during nutrient deprivation. Here, this project stored the raw sequencing data associated with this study.