Lipid droplet breakdown requires dynamin 2 for vesiculation of autolysosomal tubules in hepatocytes

Ryan J. Schulze, Shaun G. Weller, Barbara Schroeder, Eugene W. Krueger, Susan Chi, Carol A. Casey, Mark A. McNiven

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Lipid droplets (LDs) are lipid storage organelles that in hepatocytes may be catabolized by autophagy for use as an energy source, but the membrane-trafficking machinery regulating such a process is poorly characterized. We hypothesized that the large GTPase Dynamin 2 (Dyn2), well known for its involvement in membrane deformation and cellular protein trafficking, could orchestrate autophagy-mediated LD breakdown. Accordingly, depletion or pharmacologic inhibition of Dyn2 led to a substantial accumulation of LDs in hepatocytes. Strikingly, the targeted disruption of Dyn2 induced a dramatic four- to fivefold increase in the size of autolysosomes. Chronic or acute Dyn2 inhibition combined with nutrient deprivation stimulated the excessive tubulation of these autolysosomal compartments. Importantly, Dyn2 associated with these tubules along their length, and the tubules vesiculated and fragmented in the presence of functional Dyn2. These findings provide new evidence for the participation of the autolysosome in LD metabolism and demonstrate a novel role for dynamin in the function and maturation of an autophagic compartment.

Original languageEnglish (US)
Pages (from-to)315-326
Number of pages12
JournalJournal of Cell Biology
Volume203
Issue number2
DOIs
StatePublished - Oct 28 2013

ASJC Scopus subject areas

  • Cell Biology

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    Schulze, R. J., Weller, S. G., Schroeder, B., Krueger, E. W., Chi, S., Casey, C. A., & McNiven, M. A. (2013). Lipid droplet breakdown requires dynamin 2 for vesiculation of autolysosomal tubules in hepatocytes. Journal of Cell Biology, 203(2), 315-326. https://doi.org/10.1083/jcb.201306140