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

Research output: Contribution to journalArticle

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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 cellularmachinery 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.

Original languageEnglish (US)
Article number1601470
JournalScience Advances
Volume2
Issue number12
DOIs
StatePublished - Dec 2016

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Carrier Proteins
Autophagy
Guanosine
Hepatocytes
Membrane Lipids
Small Interfering RNA
Adenosine Triphosphatases
Lipid Droplets
Digestion
Lipids
Membranes
Autophagosomes

ASJC Scopus subject areas

  • General

Cite this

Li, Z., Schulze, R. J., Weller, S. G., Krueger, E. W., Schott, M. B., Zhang, X., ... McNiven, M. A. (2016). A novel rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. Science Advances, 2(12), [1601470]. https://doi.org/10.1126/sciadv.1601470

A novel rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. / Li, Zhipeng; Schulze, Ryan J.; Weller, Shaun G.; Krueger, Eugene W.; Schott, Micah B.; Zhang, Xiaodong; Casey, Carol A; Liu, Jun; Stöckli, Jacqueline; James, David E.; McNiven, Mark A.

In: Science Advances, Vol. 2, No. 12, 1601470, 12.2016.

Research output: Contribution to journalArticle

Li, Z, Schulze, RJ, Weller, SG, Krueger, EW, Schott, MB, Zhang, X, Casey, CA, Liu, J, Stöckli, J, James, DE & McNiven, MA 2016, 'A novel rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets', Science Advances, vol. 2, no. 12, 1601470. https://doi.org/10.1126/sciadv.1601470
Li Z, Schulze RJ, Weller SG, Krueger EW, Schott MB, Zhang X et al. A novel rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. Science Advances. 2016 Dec;2(12). 1601470. https://doi.org/10.1126/sciadv.1601470
Li, Zhipeng ; Schulze, Ryan J. ; Weller, Shaun G. ; Krueger, Eugene W. ; Schott, Micah B. ; Zhang, Xiaodong ; Casey, Carol A ; Liu, Jun ; Stöckli, Jacqueline ; James, David E. ; McNiven, Mark A. / A novel rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. In: Science Advances. 2016 ; Vol. 2, No. 12.
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