title: A novel Rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets.
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.
authors.affiliation: Biochemistry and Molecular Biology Program, Mayo Graduate School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.; Department of Biochemistry and Molecular Biology and the Center for Digestive Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology and the Center for Digestive Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Ryan J
authors.identifier: 0000-0001-6427-9301
authors.initials: RJ
authors.lastname: Schulze
authors.affiliation: Department of Biochemistry and Molecular Biology and the Center for Digestive Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Weller
authors.affiliation: Department of Biochemistry and Molecular Biology and the Center for Digestive Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Eugene W
authors.identifier: 0000-0002-1171-9075
authors.initials: EW
authors.lastname: Krueger
authors.affiliation: Department of Biochemistry and Molecular Biology and the Center for Digestive Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Micah B
authors.initials: MB
authors.lastname: Schott
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 E Shea Boulevard, Scottsdale, AZ 85259, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Casey
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 E Shea Boulevard, Scottsdale, AZ 85259, USA.
authors.forename: Jun
authors.identifier: 0000-0002-3646-0004
authors.initials: J
authors.lastname: Liu
authors.affiliation: Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jacqueline
authors.identifier: 0000-0002-6446-7350
authors.initials: J
authors.lastname: Stöckli
authors.affiliation: Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia.; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: David E
authors.identifier: 0000-0001-5946-5257
authors.initials: DE
authors.lastname: James
authors.affiliation: Department of Biochemistry and Molecular Biology and the Center for Digestive Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: McNiven
keywords: Autophagy; Lipid Droplet; Lipophagy; Rab GTPase