Microlipophagy from Simple to Complex Eukaryotes

Abstract

Lipophagy is a selective degradation of lipid droplets in lysosomes or vacuoles. Apart from its role in generating energy and free fatty acids for membrane repair, growth, and the formation of new membranes, lipophagy emerges as a key player in other cellular processes and disease pathogenesis. While fungal, plant, and algal cells use microlipophagy, the most prominent form of lipophagy in animal cells is macrolipophagy. However, recent studies showed that animal cells can also use microlipophagy to metabolize their lipid droplets. Therefore, to no surprise, microlipophagy is conserved from simple unicellular to the most complex multicellular eukaryotes, and many eukaryotic cells can operate both forms of lipophagy. Macrolipophagy is the most studied and better understood at the molecular level, while our understanding of microlipophagy is very sparse. This review will discuss microlipophagy from the perspective of its conservation in eukaryotes and its importance in diseases. To better appreciate the conserved nature of microlipophagy, different organisms and types of cells in which microlipophagy has been reported are also shown in a tabular form. We also point toward the gaps in our understanding of microlipophagy, including the signaling behind microlipophagy, especially in the cells of complex multicellular organisms.

Keywords: autophagy; chaperon-mediated autophagy; lipid droplets; lipophagy; macroautophagy; macrolipophagy; microautophagy; microlipophagy; selective autophagy; vacuolar microdomains.

Figure 1

Lipophagy from fungi to higher eukaryotes. Lipophagy in fungi occurs through microlipophagy. Under stress conditions, LDs are transported to the vacuolar membrane. At the vacuole, LDs interact with the raft-like vacuolar microdomains. Then, LDs are internalized by the vacuole, and microlipophagic bodies are formed inside the vacuole before their disintegration by vacuolar hydrolases. Lipophagy in plants and algae occurs through microlipophagy as well as macrolipophagy. Macrolipophagy involves a cup-like phagophore, which is an intermediate of the double-membrane autophagosome that encircles and transports LD to the vacuole. Fusion of the autophagosome with the vacuole generates the macrolipophagic body inside the vacuole, which is decomposed by vacuolar hydrolases. The extent to which plants and algae form vacuolar microdomains for microlipophagy is not yet known. Lipophagy in animals occurs through microlipophagy and macrolipophagy, which is assisted by the CMA pathway. Several LD-associated perilipins must be degraded by Hsc70- and LAMP2A-mediated CMA before the LD can be degraded by macrolipophagy. The extent to which animals form microdomains for microlipophagy is currently unknown. Created in BioRender. Arrowood, C. (2025) https://BioRender.com/m15y166 (accessed on 30 November 2024).