The importance of microlipophagy in liver.

Cytoplasmic lipid droplets (LDs) store energy in the form of esterified fatty acids. Mobilization of those fatty acids can occur through cytosolic lipases that traffic to droplets, through lipophagy, or likely through LD contact sites with other organelles. Lipophagy, the degradation of LDs by lysosomes, has two forms: macrolipophagy, involving formation of autophagosomes, trapping LDs, that then fuse with lysosomes; and microlipophagy, in which LDs are directly engulfed by lysosomes. Macrolipophagy has been well described in liver, an organ in which LDs often accumulate in obesity and other disease states. The manuscript by Schulze et al. (1) in PNAS clearly shows that microlipophagy, a process well described in yeast, is a significant pathway in isolated hepatocytes and in liver in vivo. It is not difficult to imagine this is the tip of the iceberg and that the importance of microautophagic events in mammalian cells has been underappreciated until now. LDs are composed of a neutral lipid core surrounded by a phospholipid monoleaflet into which are embedded proteins (2). The bulk of neutral lipids is usually triacyglycerols and steryl esters but may include acylceramides, retinyl esters, and other bioactive lipids. The LD surface is home to perilipins, which protect against adventitious lipolysis, and many enzymes of lipid metabolism. The surface also provides storage for histones, proteins of the innate immune system, and serves as a scaffold for the assembly of viral pathogens. While LD are valuable, they are not always benign (3). Overextended adipose tissue invites inflammation. Fatty liver disease affects a growing fraction of the population of industrialized countries, as adipose stores become saturated upon chronic overeating. Foam cells develop and accumulate during atherogenesis as macrophages feast on available external lipid, filling up their cytoplasm with LDs. Mobilization of fatty acids from LDs can quickly occur by cytosolic lipases that … [↵][1]1Email: Joel.Goodman{at}UTSouthwestern.edu. [1]: #xref-corresp-1-1