Recently, a specific peptide inhibitor for ATGL was isolated from white blood cells, specifically mononuclear cells. This peptide was originally identifed as being involved in the regulation of the G 0 to G 1 transition of the cell cycle . This peptide was, therefore, called G0G1 switch protein 2 (G0S2). The protein is found in numerous tissues, with highest concentrations in adipose tissue and liver. In adipose tissue G0S2 expression is very low during fasting but increases after feeding. Conversely, fasting or PPARα-agonists increase hepatic G0S2 expression. The protein has been shown to localize to LDs, cytoplasm, ER, and mitochondria. These different subcellular localizations likely relate to multiple functions for G0S2 in regulating lipolysis, the cell cycle , and, possibly, apoptosis via its ability to interact with the mitochondrial antiapoptotic factor Bcl-2. With respect to ATGL regulation, the binding of the enzyme to LDs and subsequent is dependent on a physical interaction between the N-terminal region of G0S2 and the patatin domain of ATGL.
ACC1 is strictly cytosolic and is enriched in liver, adipose tissue and lactating mammary tissue. ACC2 was originally discovered in rat heart but is also expressed in liver and skeletal muscle. ACC2 has an N -terminal extension that contains a mitochondrial targeting motif and is found associated with carnitine palmitoyltransferase I (CPT I) allowing for rapid regulation of CPT I by the malonyl-CoA produced by ACC. Both isoforms of ACC are allosterically activated by citrate and inhibited by palmitoyl-CoA and other short- and long-chain fatty acyl-CoAs. Citrate triggers the polymerization of ACC1 which leads to significant increases in its activity. Although ACC2 does not undergo significant polymerization (presumably due to its mitochondrial association) it is allosterically activated by citrate. Glutamate and other dicarboxylic acids can also allosterically activate both ACC isoforms.