HDAC6 regulates lipid droplet turnover in response to nutrient deprivation via p62-mediated selective autophagy

Yan Yan^{a, b, c, #},
Hao Wang^{d, #},
Chuanxian Wei^{a, b, c, #},
Yuanhang Xiang^c,
Xuehong Liang^c,
Chung-Weng Phang^{a, b},
Renjie Jiao^{a, b, c
, ,}

a.
Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
b.
The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
c.
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, The Chinese Academy of Sciences, Beijing, 100101, China
d.
Department of Chemistry and Biology, National University of Defense Technology, Changsha, 410072, China

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Corresponding author: E-mail address: rjiao@sun5.ibp.ac.cn (Renjie Jiao)

These authors contributed equally to this work.

摘要

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Abstract: Autophagy has been evolved as one of the adaptive cellular processes in response to stresses such as nutrient deprivation. Various cellular cargos such as damaged organelles and protein aggregates can be selectively degraded through autophagy. Recently, the lipid storage organelle, lipid droplet (LD), has been reported to be the cargo of starvation-induced autophagy. However, it remains largely unknown how the autophagy machinery recognizes the LDs and whether it can selectively degrade LDs. In this study, we show that Drosophila histone deacetylase 6 (dHDAC6), a key regulator of selective autophagy, is required for the LD turnover in the hepatocyte-like oenocytes in response to starvation. HDAC6 regulates LD turnover via p62/SQSTM1 (sequestosome 1)-mediated aggresome formation, suggesting that the selective autophagy machinery is required for LD recognition and degradation. Furthermore, our results show that the loss of dHDAC6 causes steatosis in response to starvation. Our findings suggest that there is a potential link between selective autophagy and susceptible predisposition to lipid metabolism associated diseases in stress conditions.
- HDAC6 /
- Lipid droplets /
- Metabolic adaption /
- p62/SQSTM1 /
- Selective autophagy
These authors contributed equally to this work.
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参考文献(54)

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