The Small GTPase Rab7 as a Central Regulator of Hepatolar Lipophagy

Schroeder, B., Schulze, R.J., Weller, S.G., Sletten, A.C., Casey, C.A. & McNiven, M.A.

Hepatology 61, 1896-1907 (2015)

Speaker: Jia-Wen Chen (陳佳文)                                         Time: 13:00~14:00, Nov. 23, 2016

Commentator: Cheung, Chun Hei Antonio (張雋曦老師)   Place: Room 601

Abstract:

Autophagy is a catabolic process with the function in the maintenance of cellular and tissue homeostasis. It allows degradation and recycling of damaged and harmful cellular components. Recently, the autophagic substrates have been extended to lipids. A novel mechanism of lipid metabolism through the autophagic degradation pathway designated as lipophagy has been reported.¹ However, the regulatory mechanism that controls this process is poorly defined. Rab7 is a conserved component of the lipid droplet (LD) membrane, and regulates the transport and maturation of the late endocytic pathway.² In this study, the authors reveal the molecular mechanism that regulates the interaction between LD and endocytic degradative compartments during starvation-induced lipophagy in hepatocytes. Rab7 is indispensable for LD breakdown (“lipophagy”) in hepatocytes under the nutrient deprivation conditions. Rab7 was activated and recruited to the membranes of LD and endolysosome under the nutrition deficiency conditions. Activated rab7 is required for promoting directly physical interactions between multivesicular bodies (MVBs)/lysosomes and LDs to form lipophagy in which activated Rab7 associates with the membranes of diverse vesicles. In summary, this study reveals the role of autophagy in hepatocellular LD catabolism, and the small GTPase Rab7 is a key regulatory component of this essential process.

References:

1         Ward, C., Martinez-Lopez, N., Otten, E.G., Carroll, B., Maetzel, D., Singh, R., Sarkar, S. & Korolchuk, V.I. Autophagy, lipophagy and lysosomal lipid storage disorders. Biochim Biophys Acta 1861, 269-284 (2016).

2          Bucci, C., Thomsen, P., Nicoziani, P., McCarthy, J. & van Deurs, B. Rab7: a key to lysosome biogenesis. Mol. Biol. Cell 11, 467-480 (2000).