Classical and alternative roles for autophagy in lipid metabolism.

Abstract

Intracellular lipid metabolism is a complex interplay of exogenous lipid handling, trafficking, storage, lipolysis, and export. Recent work has implicated the cellular degradative process called autophagy in several aspects of lipid metabolism. We will discuss both the classical and novel roles of autophagy and the autophagic machinery in this setting. The delivery of lipid droplets to lysosomes for hydrolysis, named lipophagy, was the first described functional role for autophagy in lipid metabolism. The molecular machinery and regulation of this selective form of macroautophagy is beginning to be discovered and has the potential to shed enormous light on intracellular lipolysis. Yet, the autophagic machinery appears to also be coopted for alternative roles that include interaction with cytosolic lipolysis pathways, supply and expansion of lipid droplets, and lipoprotein trafficking. Additionally, lesser studied forms of autophagy called microautophagy and chaperone-mediated autophagy have distinct roles in lipid handling that also intersect with classical macroautophagy. The integration of current knowledge in these areas into a holistic understanding of intracellular lipid metabolism will be a goal of this review. As the field of autophagy has evolved and expanded to include functional roles in various aspects of cellular degradation, so has its role in intracellular lipid metabolism. Understanding the mechanisms underlying these classical and alternative roles of autophagy will not only enhance our knowledge in lipid biology but also provide new avenues of translation to human lipid disorders.