Research Paper|Volume 16, Issue 4|pp 3257—3279

BubR1 controls starvation-induced lipolysis via IMD signaling pathway in Drosophila

Mengyou Liu^1,², Shengye Yang^1,^3,⁴, Jingsi Yang¹, Ping Feng², Feng Luo^3,⁴, Qiaoqiao Zhang¹, Li Yang⁵, Hao Jiang¹

¹Laboratory for Aging and Cancer Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
²Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
³Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
⁴Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
⁵Department of Gastroenterology and Hepatology and Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China

* Equal contribution and co-first authors

Received: July 14, 2023Accepted: January 8, 2024Published: February 8, 2024

https://doi.org/10.18632/aging.205533

Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Lipolysis, the key process releasing fat acids to generate energy in adipose tissues, correlates with starvation resistance. Nevertheless, its detail mechanisms remain elusive. BubR1, an essential mitotic regulator, ensures proper chromosome alignment and segregation during mitosis, but its physiological functions are largely unknown. Here, we use Drosophila adult fat body, the major lipid storage organ, to study the functions of BubR1 in lipolysis. We show that both whole body- and fat body-specific BubR1 depletions increase lipid degradation and shorten the lifespan under fasting but not feeding. Relish, the conserved regulator of IMD signaling pathway, acts as the downstream target of BubR1 to control the expression level of Bmm and modulate the lipolysis upon fasting. Thus, our study reveals new functions of BubR1 in starvation-induced lipolysis and provides new insights into the molecular mechanisms of lipolysis mediated by IMD signaling pathway.