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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals

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Author(s):
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Liu, Xiaojing [1] ; Cooper, Daniel E. [2] ; Cluntun, Ahmad A. [1] ; Warmoes, Marc O. [1] ; Zhao, Steven [3] ; Reid, Michael A. [1] ; Liu, Juan [1] ; Lund, Peder J. [4] ; Lopes, Mariana [4] ; Garcia, Benjamin A. [4] ; Wellen, Kathryn E. [3] ; Kirsch, David G. [1, 2] ; Locasale, Jason W. [1]
Total Authors: 13
Affiliation:
[1] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 - USA
[2] Duke Univ, Dept Radiat Oncol, Med Ctr, Durham, NC 27710 - USA
[3] Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA 19104 - USA
[4] Univ Penn, Perelman Sch Med, Penn Epigenet Inst, Dept Biochem & Biophys, Philadelphia, PA 19104 - USA
Total Affiliations: 4
Document type: Journal article
Source: Cell; v. 175, n. 2, p. 502+, OCT 4 2018.
Web of Science Citations: 21
Abstract

Acetate is a major nutrient that supports acetylcoenzyme A (Ac-CoA) metabolism and thus lipogenesis and protein acetylation. However, its source is unclear. Here, we report that pyruvate, the end product of glycolysis and key node in central carbon metabolism, quantitatively generates acetate in mammals. This phenomenon becomes more pronounced in the context of nutritional excess, such as during hyperactive glucose metabolism. Conversion of pyruvate to acetate occurs through two mechanisms: (1) coupling to reactive oxygen species (ROS) and (2) neomorphic enzyme activity from keto acid dehydrogenases that enable function as pyruvate decarboxylases. Further, we demonstrate that de novo acetate production sustains Ac-CoA pools and cell proliferation in limited metabolic environments, such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. By virtue of de novo acetate production being coupled to mitochondrial metabolism, there are numerous possible regulatory mechanisms and links to pathophysiology. (AU)

FAPESP's process: 17/15835-1 - Cross-talk between signaling pathway and histone modifications in response to growth factor stimulation
Grantee:Mariana de Camargo Lopes
Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)