Report Bub1 and Bub3 regulate metabolic adaptation via macrolipophagy in Drosophila

Lipophagy, the process of selective catabolism of lipid droplets (LDs) by autophagy, maintains lipid homeo-stasis and provides cellular energy under metabolic adaptation, yet its underlying mechanism remains largely ambiguous. Here, we show that the Bub1-Bub3 complex, the crucial regulator involved in the whole process of chromosome alignment and separation during mitosis, controls the fasting-induced lipid catabolism in the fat body (FB) of Drosophila. Bidirectional deviations of the Bub1 or Bub3 level affect the consumption of tri-acylglycerol (TAG) of fat bodies and the survival rate of adult flies under starving. Moreover, Bub1 and Bub3 work together to attenuate lipid degradation via macrolipophagy upon fasting. Thus, we uncover physiolog-ical roles of the Bub1-Bub3 complex on metabolic adaptation and lipid metabolism beyond their canonical mitotic functions, providing insights into the in vivo functions and molecular mechanisms of macrolipophagy during nutrient deprivation.

Automated summary

The Bub1-Bub3 complex, known for its role in chromosome alignment and separation during mitosis, is shown to regulate lipid degradation in the fat body of Drosophila. Levels of Bub1 or Bub3 affect tri-acylglycerol consumption and fly survival under starvation. This study reveals novel physiological roles of the Bub1-Bub3 complex in metabolic adaptation and lipid metabolism beyond mitotic functions.