Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals.

Published

Journal Article

Acetate is a major nutrient that supports acetyl-coenzyme 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.

Full Text

Duke Authors

Cited Authors

  • Liu, X; Cooper, DE; Cluntun, AA; Warmoes, MO; Zhao, S; Reid, MA; Liu, J; Lund, PJ; Lopes, M; Garcia, BA; Wellen, KE; Kirsch, DG; Locasale, JW

Published Date

  • October 4, 2018

Published In

Volume / Issue

  • 175 / 2

Start / End Page

  • 502 - 513.e13

PubMed ID

  • 30245009

Pubmed Central ID

  • 30245009

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2018.08.040

Language

  • eng

Conference Location

  • United States