The perilipin family of lipid droplet proteins: Gatekeepers of intracellular lipolysis

Abstract

Lipid droplets in chordates are decorated by two or more members of the perilipin family of lipid droplet surface proteins. The perilipins sequester lipids by protecting lipid droplets from lipase action. Their relative expression and protective nature is adapted to the balance of lipid storage and utilization in specific cells. Most cells of the body have tiny lipid droplets with perilipins 2 and 3 at the surfaces, whereas specialized fat-storing cells with larger lipid droplets also express perilipins 1, 4, and/or 5. Perilipins 1, 2, and 5 modulate lipolysis by controlling the access of lipases and co-factors of lipases to substrate lipids stored within lipid droplets. Although perilipin 2 is relatively permissive to lipolysis, perilipins 1 and 5 have distinct control mechanisms that are altered by phosphorylation. Here we evaluate recent progress toward understanding functions of the perilipins with a focus on their role in regulating lipolysis and autophagy.

Connecting pancreatic islet lipid metabolism with insulin secretion and the development of type 2 diabetes

“…General knowledge of LD from studies of nonbeta cells LD are an intracellular organelle consisting of a neutral lipid core of TG and sterol esters (cholesterol 123 Interacts with ATGL and HSL in a PKA-dependent manner to increase lipolysis. 123 …”

“…110 Has one PKA consensus site, and PKA-mediated phosphorylation increases lipolysis. 123 Phosphorylation also promotes nuclear translocation and activation of PGC-1alpha. 139 Associates with mitochondria.…”

“…122 The best characterized function of LD is to regulate mobilization of stored lipids through interaction with lipases and lysosomes (autophagy), as recently reviewed. 60,123 LD are coated with Rab proteins and are mobile within cells. High-resolution imaging of mouse embryonic fibroblasts labeled with a fluorescent fatty acid probe revealed that LD serve as a shuttle to transfer FA from lysosomes to the mitochondria.…”

“…134 Unlike PLIN1 that regulates lipolysis through protein kinase A (PKA)-dependent interaction with HSL, PLIN2 does not have a known association with lipases or a consensus site for phosphorylation by PKA, and it is considered to serve as a passive barrier for lipolysis. 123 In nonbeta cells, the modulation of PLIN2 expression is reported to affect multiple aspects of cellular lipid handling, including FA uptake, beta-oxidation, and activation of nuclear receptors in the liver, heart, macrophages, and white adipocytes. 123 In nonbeta cells, the modulation of PLIN2 expression is reported to affect multiple aspects of cellular lipid handling, including FA uptake, beta-oxidation, and activation of nuclear receptors in the liver, heart, macrophages, and white adipocytes.…”

Lipid droplet autophagy during energy mobilization lipid homeostasis and protein quality control

“…This results in the phosphorylation of cytosolic neutral lipid lipases (adipose triglyceride lipase, ATGL and hormone sensitive lipase, HSL), and of perilipins (PLIN), a conserved family of proteins that serve as scaffolds and regulators on the LD surface (13). ATGL and HSL are then recruited to PLIN proteins on LDs where they catalyze the breakdown of neutral lipids within LDs to generate FFAs that are released from LDs (14). …”