Lipophagy

Lipophagy is the specialized form of selective macroautophagy responsible for the degradation of intracellular lipid droplets (LDs). This process involves the sequestration of LDs within double-membraned autophagosomes, which then fuse with lysosomes to allow acidic lipases, such as lysosomal acid lipase (LAL), to break down triglycerides and cholesterol esters into free fatty acids (Singh et al., 2009). Primarily regulated by nutrient-sensing pathways like mTOR and AMPK, lipophagy plays a critical role in maintaining cellular energy homeostasis and preventing lipid toxicity. Impairment of this pathway is heavily implicated in metabolic disorders, particularly nonalcoholic fatty liver disease (NAFLD/MASLD) and atherosclerosis, where excessive lipid accumulation leads to cellular dysfunction and inflammation (Zhang et al., 2018). While no drugs currently target lipophagy with absolute specificity, various autophagy modulators and metabolic regulators, such as rapamycin and metformin, are being investigated for their ability to enhance this process as a therapeutic strategy for steatotic and metabolic diseases (Ward et al., 2016).

Other names

Selective autophagy of lipid dropletsAutophagic lipid degradationMacrolipophagyLipid droplet autophagy

Induction of macroautophagy via mTOR inhibition or AMPK activation, leading to the sequestration of lipid droplets within autophagosomes and their subsequent delivery to lysosomes for degradation by lysosomal acid lipase (Singh et al., 2009; Ward et al., 2016).