Protein-protein interactions regulate the activity of Adipose Triglyceride Lipase in intracellular lipolysis

• Published in: Biochimie Vol. 169; pp. 62 - 68
• Main Authors: Kulminskaya, Natalia, Oberer, Monika
• Format: Journal Article
• Language: English
• Published: France Elsevier B.V 01.02.2020
• Subjects: ATGL; CGI-58; G0S2; HILPDA; Lipolysis; G0S2; CGI-58; ATGL; Lipolysis; HILPDA
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2019.08.004

Carefully regulated lipid homeostastis generates an optimal physiological, non-toxic environment. Imbalances in lipid metabolism lead to obesity and are associated with type-2 diabetes, hepatic steatosis, hypertension and cardiovascular disease. Mammals store energy in lipid droplets predominantly in white adipose tissue. This energy reservoir builds up during periods of energy excess and is mobilized during energy deprivation. Triacylglycerols (TAGs) are unable to cross cell membranes for cell nutrition; they have to be cleaved before further transportation within the body. Lipolysis describes the cleavage of TAG and is carried out with the help of lipases. Adipose triglyceride lipase (ATGL) catalyzes the first step of intracellular lipolysis to mobilize TAG stores. In this minireview, we set the focus on molecular mechanism and interfaces behind co-activation and inhibition of ATGL, namely via its regulation by the co-activating protein CGI-58, the inhibitory proteins G0S2 and HILPDA, as well as the regulatory effect of fatty acid binding proteins and the perilipin protein family. •Protein-protein interactions play a key role in the first step of intracellular lipolysis.•Proper localization of lipolytic proteins on the surface of lipid droplet is critical.•Hydrophobic regions of G0S2 and HILPDA mediate ATGL inhibition and down-regulation.•Variants with amino acid exchanges and truncations provide insights in the interaction faces with proteins and lipids.•Further structural and mechanistic studies on lipolytic proteins and the entire lipolysome are high on demand.