A novel Rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets
Zhipeng Li,Ryan J. Schulze,Shaun G. Weller,Eugene W. Krueger,Micah B. Schott,Xiaodong Zhang,Carol A. Casey,Jun Liu,Jacqueline Stöckli,David E. James,Mark A. McNiven +10 more
TL;DR: A novel function for a small Rab guanosine triphosphatase (GTPase) in the recruitment of adaptors required for the engulfment of LDs by the growing autophagosome is reported.
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Abstract: The autophagic digestion of lipid droplets (LDs) through lipophagy is an essential process by which most cells catabolize lipids as an energy source. However, the cellular machinery used for the envelopment of LDs during autophagy is poorly understood. We report a novel function for a small Rab guanosine triphosphatase (GTPase) in the recruitment of adaptors required for the engulfment of LDs by the growing autophagosome. In hepatocytes stimulated to undergo autophagy, Rab10 activity is amplified significantly, concomitant with its increased recruitment to nascent autophagic membranes at the LD surface. Disruption of Rab10 function by small interfering RNA knockdown or expression of a GTPase-defective variant leads to LD accumulation. Finally, Rab10 activation during autophagy is essential for LC3 recruitment to the autophagosome and stimulates its increased association with the adaptor protein EHBP1 (EH domain binding protein 1) and the membrane-deforming adenosine triphosphatase EHD2 (EH domain containing 2) that, together, are essential in driving the activated “engulfment” of LDs during lipophagy in hepatocytes.
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Citations
Direct lysosome-based autophagy of lipid droplets in hepatocytes
Ryan J. Schulze,Eugene W. Krueger,Shaun G. Weller,Katherine M. Johnson,Carol A. Casey,Micah B. Schott,Mark A. McNiven +6 more
TL;DR: This work uses live-cell and electron microscopy to demonstrate that stable contacts between LDs and lysosomes in hepatocytes can result in the transfer of both proteins and lipids from LDs directly into the lysOSome in the absence of an autophagosomal intermediate.
188
The cell biology of the hepatocyte: A membrane trafficking machine.
Ryan J. Schulze,Micah B. Schott,Carol A. Casey,Carol A. Casey,Pamela L. Tuma,Mark A. McNiven +5 more
TL;DR: The liver performs numerous vital functions, including the detoxification of blood before access to the brain while simultaneously secreting and internalizing scores of proteins and lipids to maintain appropriate blood chemistry.
Autophagy in hepatic adaptation to stress
TL;DR: The importance of functional Autophagy for hepatic physiology, as well as the mechanisms whereby defects in autophagy cause liver disease are critically discussed.
145
Hepatic lipid droplet homeostasis and fatty liver disease.
TL;DR: How triglyceride and phospholipid homeostasis are regulated in hepatocytes and how imbalances between lipid storage, degradation and lipoprotein secretion lead to non-alcoholic fatty liver disease are reviewed.
138
The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders
Shuang Zhang,Xueqiang Peng,Shuo Yang,Xinyu Li,Ming-Lih Huang,Shibo Wei,Jiaxing Liu,Guangpeng He,Hongyu Zheng,Liang Wang,Han Li,Qing Fan +11 more
TL;DR: The role of lipophagy in cancer and other human diseases is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets as mentioned in this paper .
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