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Maturation of Lipophagic Organelles in Hepatocytes Is Dependent Upon a Rab10/Dynamin‐2 Complex
Author(s) -
Li Zhipeng,
Weller Shaun G.,
DrizyteMiller Kristina,
Chen Jing,
Krueger Eugene W.,
Mehall Bridget,
Stöckli Jacqueline,
Casey Carol A.,
Cao Hong,
McNiven Mark A.
Publication year - 2020
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31059
Subject(s) - rab , gtpase , microbiology and biotechnology , autophagy , dynamin , organelle , biology , cytoplasm , lipid droplet , effector , cell , biochemistry , endocytosis , apoptosis
Background and Aims Hepatocytes play a central role in storage and utilization of fat by the liver. Selective breakdown of lipid droplets (LDs) by autophagy (also called lipophagy) is a key process utilized to catabolize these lipids as an energy source. How the autophagic machinery is selectively targeted to LDs, where it mediates membrane engulfment and subsequent degradation, is unclear. Recently, we have reported that two distinct GTPases, the mechanoenzyme, dynamin2 (Dyn2), and the small regulatory Rab GTPase, Rab10, work independently at distinct steps of lipophagy in hepatocytes. Approach and Results In an attempt to understand how these proteins are regulated and recruited to autophagic organelles, we performed a nonbiased biochemical screen for Dyn2‐binding partners and found that Dyn2 actually binds Rab10 directly through a defined effector domain of Rab10 and the middle domain of Dyn2. These two GTPases can be observed to interact transiently on membrane tubules in hepatoma cells and along LD‐centric autophagic membranes. Most important, we found that a targeted disruption of this interaction leads to an inability of cells to trim tubulated cytoplasmic membranes, some of which extend from lipophagic organelles, resulting in LD accumulation.Conclusions This study identifies a functional, and direct, interaction between Dyn2 and a regulatory Rab GTPase that may play an important role in hepatocellular metabolism.