Biogenesis and Breakdown of Lipid Droplets in Pathological Conditions

FADER KAISER, CLAUDIO M.; ROMANO, PATRICIA S.; VANRELL, M. CRISTINA; POCOGNONI, CRISTIAN A.; JACOB, JULIETA; CARUSO, BENJAMÍN; DELGUI, LAURA R.

Frontiers in Cell and Developmental Biology

Frontiers media SA

Año: 2022 vol. 9

Lipid droplets (LD) have long been considered as mere fat drops; however, LD have latelybeen revealed to be ubiquitous, dynamic and to be present in diverse organelles in whichthey have a wide range of key functions. Although incompletely understood, the biogenesisof eukaryotic LD initiates with the synthesis of neutral lipids (NL) by enzymes located in theendoplasmic reticulum (ER). The accumulation of NL leads to their segregation intonanometric nuclei which then grow into lenses between the ER leaflets as they arefurther filled with NL. The lipid composition and interfacial tensions of both ER and thelenses modulate their shape which, together with specific ER proteins, determine theproneness of LD to bud from the ER toward the cytoplasm. The most important function ofLD is the buffering of energy. But far beyond this, LD are actively integrated intophysiological processes, such as lipid metabolism, control of protein homeostasis,sequestration of toxic lipid metabolic intermediates, protection from stress, andproliferation of tumours. Besides, LD may serve as platforms for pathogen replicationand defense. To accomplish these functions, from biogenesis to breakdown, eukaryoticLD have developed mechanisms to travel within the cytoplasm and to establish contactwith other organelles. When nutrient deprivation occurs, LD undergo breakdown (lipolysis),which begins with the LD-associated members of the perilipins family PLIN2 andPLIN3 chaperone-mediated autophagy degradation (CMA), a specific type ofautophagy that selectively degrades a subset of cytosolic proteins in lysosomes.Indeed, PLINs CMA degradation is a prerequisite for further true lipolysis, whichoccurs via cytosolic lipases or by lysosome luminal lipases when autophagosomesengulf portions of LD and target them to lysosomes. LD play a crucial role in severalpathophysiological processes. Increased accumulation of LD in non-adipose cells iscommonly observed in numerous infectious diseases caused by intracellularpathogens including viral, bacterial, and parasite infections, and is gradually recognizedas a prominent characteristic in a variety of cancers. This review discusses currentevidence related to the modulation of LD biogenesis and breakdown caused byintracellular pathogens and cancer.