The importance of microlipophagy in liver

Joel M. Goodman

PNAS January 12, 2021 118 (2) e2024058118

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.

See https://www.pnas.org/content/118/2/e2024058118

Figure: Pathways of LD digestion in liver cells. 1) Upon metabolic need, the size of LDs may first be reduced by cytosolic lipases initiated by adipocyte triglyceride lipase. They then are subjected to one of two autophagic pathways. 2a) Phagophore formation around LDs initiates macrolipophagy, resulting in fusion of the lipophagosome with a lysosome. 2b) Alternatively, as shown by Schulze et al. (1), an LD may be attracted directly to a lysosome, often resulting in macrolipophagy in which injection of LD contents into the lysosome occurs, or the entire LD is engulfed (not shown)