An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

Figure 3

Schematic model representing the mechanisms of PLIN1 and PLIN2 action and PLIN3, PLIN4, and PLIN5 localization. In basal conditions (left panel), PLIN1 forms a complex with CGI-58, while ATGL association with G0S2 impairs the enzyme activity. PLIN1 and PLIN 2 block the LD access to lipases, and only a low rate of lipolysis takes place. Under lipogenic stimuli or FA surplus (central panel), PLIN2, PLIN3, and PLIN4 localize on nascent LDs at ER. Lipolytic stimuli (right panel), such as β-adrenergic stimulation, activate PKA via increased levels of cAMP. PKA phosphorylates PLIN1 and HSL, inducing HSL translocation to LD surface and release of CGI-58. This latter can form a complex with ATGL, whose activity also requires the binding with GBF1 factor and with Arf/COPI complex resulting in activated lipolysis. GBF1: Golgi brefeldin A resistance guanine nucleotide exchange factor 1; G052: 33mer gliadin peptide; CGI-58: comparative gene identification-58; P1: perilipin 1; P2: perilipin 2; P3: perilipin 3; P4: perilipin 4; P5: perilipin 5; PKA: protein kinase A; Arf1/COPI: ADP ribosylation factor/coat protein complex.