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The recent insights into the function of ACAT1: A possible anti-cancer therapeutic target.
Life Sci 2019; 232:116592LS

Abstract

Acetoacetyl-CoA thiolase also known as acetyl-CoA acetyltransferase (ACAT) corresponds to two enzymes, one cytosolic (ACAT2) and one mitochondrial (ACAT1), which is thought to catalyse reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA during ketogenesis and ketolysis respectively. In addition to this activity, ACAT1 is also involved in isoleucine degradation pathway. Deficiency of ACAT1 is an inherited metabolic disorder, which results from a defect in mitochondrial acetoacetyl-CoA thiolase activity and is clinically characterized with patients presenting ketoacidosis. In this review I discuss the recent findings, which unexpectedly expand the known functions of ACAT1, indicating a role for ACAT1 well beyond its classical activity. Indeed ACAT1 has recently been shown to possess an acetyltransferase activity capable of specifically acetylating Pyruvate DeHydrogenase (PDH), an enzyme involved in producing acetyl-CoA. ACAT1-dependent acetylation of PDH was shown to negatively regulate this enzyme with a consequence in Warburg effect and tumor growth. Finally, the elevated ACAT1 enzyme activity in diverse human cancer cell lines was recently reported. These important novel findings on ACAT1's function and expression in cancer cell proliferation point to ACAT1 as a potential new anti-cancer target.

Authors+Show Affiliations

Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Afsaneh.goudarzi@sbmu.ac.ir.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31228515

Citation

Goudarzi, Afsaneh. "The Recent Insights Into the Function of ACAT1: a Possible Anti-cancer Therapeutic Target." Life Sciences, vol. 232, 2019, p. 116592.
Goudarzi A. The recent insights into the function of ACAT1: A possible anti-cancer therapeutic target. Life Sci. 2019;232:116592.
Goudarzi, A. (2019). The recent insights into the function of ACAT1: A possible anti-cancer therapeutic target. Life Sciences, 232, p. 116592. doi:10.1016/j.lfs.2019.116592.
Goudarzi A. The Recent Insights Into the Function of ACAT1: a Possible Anti-cancer Therapeutic Target. Life Sci. 2019 Sep 1;232:116592. PubMed PMID: 31228515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The recent insights into the function of ACAT1: A possible anti-cancer therapeutic target. A1 - Goudarzi,Afsaneh, Y1 - 2019/06/19/ PY - 2019/04/13/received PY - 2019/06/18/revised PY - 2019/06/18/accepted PY - 2019/6/23/pubmed PY - 2019/6/23/medline PY - 2019/6/23/entrez KW - Acetyl-CoA acetyltransferase (ACAT) KW - Ketogenesis KW - Ketolysis KW - Post-translational modifications SP - 116592 EP - 116592 JF - Life sciences JO - Life Sci. VL - 232 N2 - Acetoacetyl-CoA thiolase also known as acetyl-CoA acetyltransferase (ACAT) corresponds to two enzymes, one cytosolic (ACAT2) and one mitochondrial (ACAT1), which is thought to catalyse reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA during ketogenesis and ketolysis respectively. In addition to this activity, ACAT1 is also involved in isoleucine degradation pathway. Deficiency of ACAT1 is an inherited metabolic disorder, which results from a defect in mitochondrial acetoacetyl-CoA thiolase activity and is clinically characterized with patients presenting ketoacidosis. In this review I discuss the recent findings, which unexpectedly expand the known functions of ACAT1, indicating a role for ACAT1 well beyond its classical activity. Indeed ACAT1 has recently been shown to possess an acetyltransferase activity capable of specifically acetylating Pyruvate DeHydrogenase (PDH), an enzyme involved in producing acetyl-CoA. ACAT1-dependent acetylation of PDH was shown to negatively regulate this enzyme with a consequence in Warburg effect and tumor growth. Finally, the elevated ACAT1 enzyme activity in diverse human cancer cell lines was recently reported. These important novel findings on ACAT1's function and expression in cancer cell proliferation point to ACAT1 as a potential new anti-cancer target. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31228515/The_recent_insights_into_the_function_of_ACAT1:_A_possible_anti-cancer_therapeutic_target L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30518-1 DB - PRIME DP - Unbound Medicine ER -