Classical and alternative roles for autophagy in lipid metabolism

Abstract

Purpose of review 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. Recent findings 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. Summary 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.

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

“…Interestingly, the lipid profile of cultured Atg7 deficient keratinocytes is also altered compared controls, but the change in the proportions of the lipid classes examined in that study (sterols, FFA, and TG) is quite different to those which we find in sebum. This once again demonstrates that the effects of autophagy inhibition with regard to lipid metabolism is very context dependent, as has been demonstrated on numerous occasions (see for instance Refs ).…”

“…Apart from other growth factor‐mediated mechanisms which lead to SG enlargement, such as direct effects of Epigen, an Nrf2 target gene, EGFR or amphiregulin, alterations of lipolysis, lipogenesis and/or lipid metabolism are also possible pathways, and autophagy has been implicated in the first two of these processes, as well as in lipoprotein trafficking (reviewed recently in Ref. ). In addition, Pparγ, a lipid‐activated nuclear transcription factor, plays an important role in sebum production, sebaceous gland differentiation and lipid metabolism .…”

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

“…Furthermore, the initiation of autophagy is commonly associated with lipid droplet inclusion into autophagosomes and subsequent degradation by lysosomes (lipophagy) [ 54 , 55 ]; however, in this study an accumulation of lipid droplets was observed. The small guanosine triphosphatase Rab7 is indispensable for lipophagy [ 56 ] and is associated with lipid droplets and lysosomes under starvation conditions [ 57 ]. When Rab7 is silenced, there is an accumulation of lipid droplets [ 56 ].…”

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“…This product is then actively exported out of lysosomal compartment through Niemann-Pick-type C1 protein. Several lysosomal proteins such as acid sphingomyelinase (ASM), mucolipin-1, and H + -ATPase regulate metabolism and transport of cholesterol in lysosomes [62].…”