ACOT12

Last update 08 May 2025

Basic Info

Synonyms

Acetyl-coenzyme A thioesterase, ACOT12, Acyl-CoA thioester hydrolase 12

+ [10]

Introduction

Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16951743). Preferentially hydrolyzes acetyl-CoA (PubMed:16951743).

100 Clinical Results associated with ACOT12

100 Translational Medicine associated with ACOT12

0 Patents (Medical) associated with ACOT12

Literatures (Medical) associated with ACOT12

28 Aug 2024·Biochemical Society Transactions

Structure, function, and lipid sensing activity in the thioesterase superfamily

Review

Author: Ortlund, Eric A. ; Little, Molly

Lipid synthesis and transport are essential for energy, production of cell membrane, and cell signaling. Acyl-CoA thioesterases (ACOTs) function to regulate intracellular levels of fatty acyl-CoAs through hydrolysis. Two members of this family, ACOT11 and ACOT12, contain steroidogenic acute regulatory related lipid transfer domains, which typically function as lipid transport or regulatory domains. This work reviews ACOT11 and ACOT12 structures and functions, and the potential role of the START domains in lipid transfer activity and the allosteric regulation of catalytic activity.

30 Oct 2023·eLife

Hepatic conversion of acetyl-CoA to acetate plays crucial roles in energy stress.

Article

Author: Ma, Huanhuan ; Zhuo, Yue ; Wang, Jinyang ; Ouyang, Cong ; Lin, Donghai ; Wen, Yaxin ; Li, Qinxi ; Wang, Huihui ; Lin, Furong ; Feng, Liubin ; Shi, Xiulin ; Huang, Huiying ; Yao, Lizheng ; Zhang, Yan ; Zhao, Wentao ; Jiang, Bin

Accumulating evidence indicates that acetate is increased under energy stress conditions such as those that occur in diabetes mellitus and prolonged starvation. However, how and where acetate is produced and the nature of its biological significance are largely unknown. We observed overproduction of acetate to concentrations comparable to those of ketone bodies in patients and mice with diabetes or starvation. Mechanistically, ACOT12 and ACOT8 are dramatically upregulated in the liver to convert free fatty acid-derived acetyl-CoA to acetate and CoA. This conversion not only provides a large amount of acetate, which preferentially fuels the brain rather than muscle, but also recycles CoA, which is required for sustained fatty acid oxidation and ketogenesis. We suggest that acetate is an emerging novel 'ketone body' that may be used as a parameter to evaluate the progression of energy stress.

01 Jul 2023·Cancer Letters

Acyl-CoA thioesterase 12 suppresses YAP-mediated hepatocarcinogenesis by limiting glycerolipid biosynthesis

Article

Author: Ortlund, Eric A ; Acuña, Mariana ; Sugiyama, Akiko ; Hagen, Susan J ; Snyder, Nathaniel W ; He, Haiyue ; Teneche, Marcos G ; Goessling, Wolfram ; Najafi-Shoushtari, S Hani ; Cohen, David E ; Maner-Smith, Kristal M ; Liu, Xiaowei

Cancer cells use acetate to support the higher demand for energy and lipid biosynthesis during uncontrolled cell proliferation, as well as for acetylation of regulatory proteins. Acyl-CoA thioesterase 12 (Acot12) is the enzyme that hydrolyzes acetyl-CoA to acetate in liver cytosol and is downregulated in hepatocellular carcinoma (HCC). A mechanistic role for Acot12 in hepatocarcinogenesis was assessed in mice in response to treatment with diethylnitrosamine(DEN)/carbon tetrachloride (CCl₄) administration or prolonged feeding of a diet that promotes non-alcoholic steatohepatitis (NASH). Relative to controls, Acot12^-/- mice exhibited accelerated liver tumor formation that was characterized by the hepatic accumulation of glycerolipids, including lysophosphatidic acid (LPA), and that was associated with reduced Hippo signaling and increased yes-associated protein (YAP)-mediated transcriptional activity. In Acot12^-/- mice, restoration of hepatic Acot12 expression inhibited hepatocarcinogenesis and YAP activation, as did knockdown of hepatic YAP expression. Excess LPA produced due to deletion of Acot12 signaled through LPA receptors (LPARs) coupled to Gα12/13 subunits to suppress YAP phosphorylation, thereby promoting its nuclear localization and transcriptional activity. These findings identify a protective role for Acot12 in suppressing hepatocarcinogenesis by limiting biosynthesis of glycerolipids including LPA, which preserves Hippo signaling.

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ACOT12

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