Schematic overview of the regulation of ATGL on the LD. In basal condition of
lipolysis, the LD is decorated with perilipins (Plins) and cell death activator
CIDE-3 (CIDEC) to restrict the access of ATGL to the TG stores of the LD. The
additional role of Plin1 is to sequester the co-activator protein comparative
gene identification 58 (CGI-58) preventing its stimulating interaction with
ATGL. ATGL hydrolyzes TG to DG and FA which also takes place to a small extent
in basal conditions. Upon hormonal stimulation, the phosphorylation of Plin1,
Plin2, CGI-58 and ATGL leads to a change on the surface of the LD: The chaperone
heat shock protein HSPA8/hsc70 (HSPA8) shuttles Plin2 and Plin3 to the
proteasome for degradation. The dissociation of CGI-58 from Plin1 enables its
interaction with ATGL, which activates ATGL’s TG hydrolyzing activity. In
both, basal and stimulated state of lipolysis, ATGL can be inhibited by the
protein G0/G1 switch gene 2 (G0S2), acyl-CoA and synthetic inhibitor Atglistatin
(which is effective in murine ATGL only).