Signaling and other functions of lipids in autophagy: a review
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(2020) 19:214
REVIEW
Open Access
Signaling and other functions of lipids in autophagy: a review Alejandro Soto-Avellaneda1
and Brad E. Morrison1,2*
Abstract The process of autophagy is integral to cellular function. In this process, proteins, organelles, and metabolites are engulfed in a lipid vesicle and trafficked to a lysosome for degradation. Its central role in protein and organelle homeostasis has piqued interest for autophagy dysfunction as a driver of pathology for a number of diseases including cancer, muscular disorders, neurological disorders, and non-alcoholic fatty liver disease. For much of its history, the study of autophagy has centered around proteins, however, due to advances in mass spectrometry and refined methodologies, the role of lipids in this essential cellular process has become more apparent. This review discusses the diverse endogenous lipid compounds shown to mediate autophagy. Downstream lipid signaling pathways are also reviewed in the context of autophagy regulation. Specific focus is placed upon the Mammalian Target of Rapamycin (mTOR) and Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathways as integration hubs for lipid regulation of autophagy. Keywords: Autophagy, Lipids, Mammalian target of rapamycin, Peroxisome proliferator-activated receptor, Fatty acids, Phospholipids, Sphingolipids
Introduction Autophagy is a process by which proteins, organelles, and metabolites are broken down and turned over often as a response to starvation or as a means to protect the cell from damage. Autophagy pathways come in three forms, macroautophagy, microautophagy, and chaperonemediated autophagy [1]. Of these, macroautophagy is the best characterized and most well understood. Macroautophagy (hereafter referred to as autophagy) was originally studied in yeast and involves the formation of lipid vesicles known as autophagosomes that engulf cargo to be degraded. Once formed, the autophagosome is trafficked to a lysosome and a fusion event occurs resulting in the degradation of the cargo within the autophagosome (Fig. 1) [1]. Autophagy is delineated into key events: initiation, nucleation, elongation and formation of a mature * Correspondence: [email protected] 1 Biomolecular Sciences Graduate programs, Boise State University, Boise, ID 83725, USA 2 Department of Biological Sciences, Boise State University, Boise, ID 83725, USA
autophagosome, fusion of the autophagosome with a lysosome, and degradation of cargo. The initiation of autophagy is tightly regulated by the mTOR complex 1 [2]. When the cell is in a nutrient-rich state, mTORC1 is active and autophagy is suppressed, however, during nutrient-poor conditions, mTOR is inhibited which allows for the formation of Unc-51 like kinase (ULK) initiation complex composed of ULK kinases, autophagyrelated protein 13 (Atg13), Autophagy related protein 101 (Atg101), and RB1-inducible coiled-coil protein 1 (FIP200) [3]. Furthermore, ULK-1 also activates a second complex composed of Beclin1-vacuolar protein sorting protein 34
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