The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders

Abstract

Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.

Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation

“…This supports the hypothesis that the TREM2 receptor is required for lipid droplets biogenesis and to buffer cholesterol-mediated toxicity in mouse and human microglia. Another possible interpretation of our findings, is that lysosomal dysfunction in NHD iMGLs would lead to an altered degradation of these lipidic structures [96].…”

Reinventing the Penumbra — the Emerging Clockwork of a Multi-modal Mechanistic Paradigm

“…Similarly, other damaged organelles are degraded by endoplasmic reticulum (ER)-phagy [154,155] or ribophagy [156]. Lipophagy is a type of selective autophagy where denatured lipids are stored in lipid droplets and serve as substrate for β-oxidation, contributing to the energy homeostasis [157]. Aggregated proteins, as can be observed in neurodegenerative diseases, are cleared by aggrephagy via ubiquitination and autophagosomal translocation [158].…”

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

“…Autophagy can selectively and precisely target multiple cell compartments almost simultaneously, including mitochondria, endoplasmic reticulum, peroxisomes, nucleus, lysosomes, and even other cellular organelles such as fat droplets and accumulates, to maintain cell stability under both normal and abnormal conditions [ 13 , 14 ]. Many studies have individually examined macroautophagy, targeted autophagy, and autophagy regulators to broaden our knowledge of how autophagy functions in PC [ 15 , 16 ]. This review focuses on the role of autophagy in PC tumor formation, aggressiveness, and medicinal weaknesses.…”