Acetyl-CoA and the regulation of metabolism: Mechanisms and consequences

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Acetyl-CoA represents a key node in metabolism due to its intersection with many metabolic pathways and transformations. Emerging evidence reveals that cells monitor the levels of acetyl-CoA as a key indicator of their metabolic state, through distinctive protein acetylation modifications dependent on this metabolite. We offer the following conceptual model for understanding the role of this sentinel metabolite in metabolic regulation. High nucleocytosolic acetyl-CoA amounts are a signature of a 'growth' or 'fed' state and promote its utilization for lipid synthesis and histone acetylation. In contrast, under 'survival' or 'fasted' states, acetyl-CoA is preferentially directed into the mitochondria to promote mitochondrial-dependent activities such as the synthesis of ATP and ketone bodies. Fluctuations in acetyl-CoA within these subcellular compartments enable the substrate-level regulation of acetylation modifications, but also necessitate the function of sirtuin deacetylases to catalyze removal of spontaneous modifications that might be unintended. Thus, understanding the sources, fates, and consequences of acetyl-CoA as a carrier of two-carbon units has started to reveal its underappreciated but profound influence on the regulation of numerous life processes.

Original languageEnglish (US)
Pages (from-to)125-131
Number of pages7
JournalCurrent Opinion in Cell Biology
Volume33
DOIs
StatePublished - Apr 1 2015

Fingerprint

Acetyl Coenzyme A
Acetylation
Ketone Bodies
Metabolic Networks and Pathways
Histones
Mitochondria
Carbon
Adenosine Triphosphate
Lipids
Growth
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Acetyl-CoA and the regulation of metabolism : Mechanisms and consequences. / Shi, Lei; Tu, Benjamin P.

In: Current Opinion in Cell Biology, Vol. 33, 01.04.2015, p. 125-131.

Research output: Contribution to journalArticle

@article{99cd7b9fa64b4da4b16a25986494c8e6,
title = "Acetyl-CoA and the regulation of metabolism: Mechanisms and consequences",
abstract = "Acetyl-CoA represents a key node in metabolism due to its intersection with many metabolic pathways and transformations. Emerging evidence reveals that cells monitor the levels of acetyl-CoA as a key indicator of their metabolic state, through distinctive protein acetylation modifications dependent on this metabolite. We offer the following conceptual model for understanding the role of this sentinel metabolite in metabolic regulation. High nucleocytosolic acetyl-CoA amounts are a signature of a 'growth' or 'fed' state and promote its utilization for lipid synthesis and histone acetylation. In contrast, under 'survival' or 'fasted' states, acetyl-CoA is preferentially directed into the mitochondria to promote mitochondrial-dependent activities such as the synthesis of ATP and ketone bodies. Fluctuations in acetyl-CoA within these subcellular compartments enable the substrate-level regulation of acetylation modifications, but also necessitate the function of sirtuin deacetylases to catalyze removal of spontaneous modifications that might be unintended. Thus, understanding the sources, fates, and consequences of acetyl-CoA as a carrier of two-carbon units has started to reveal its underappreciated but profound influence on the regulation of numerous life processes.",
author = "Lei Shi and Tu, {Benjamin P.}",
year = "2015",
month = "4",
day = "1",
doi = "10.1016/j.ceb.2015.02.003",
language = "English (US)",
volume = "33",
pages = "125--131",
journal = "Current Opinion in Cell Biology",
issn = "0955-0674",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Acetyl-CoA and the regulation of metabolism

T2 - Mechanisms and consequences

AU - Shi, Lei

AU - Tu, Benjamin P.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Acetyl-CoA represents a key node in metabolism due to its intersection with many metabolic pathways and transformations. Emerging evidence reveals that cells monitor the levels of acetyl-CoA as a key indicator of their metabolic state, through distinctive protein acetylation modifications dependent on this metabolite. We offer the following conceptual model for understanding the role of this sentinel metabolite in metabolic regulation. High nucleocytosolic acetyl-CoA amounts are a signature of a 'growth' or 'fed' state and promote its utilization for lipid synthesis and histone acetylation. In contrast, under 'survival' or 'fasted' states, acetyl-CoA is preferentially directed into the mitochondria to promote mitochondrial-dependent activities such as the synthesis of ATP and ketone bodies. Fluctuations in acetyl-CoA within these subcellular compartments enable the substrate-level regulation of acetylation modifications, but also necessitate the function of sirtuin deacetylases to catalyze removal of spontaneous modifications that might be unintended. Thus, understanding the sources, fates, and consequences of acetyl-CoA as a carrier of two-carbon units has started to reveal its underappreciated but profound influence on the regulation of numerous life processes.

AB - Acetyl-CoA represents a key node in metabolism due to its intersection with many metabolic pathways and transformations. Emerging evidence reveals that cells monitor the levels of acetyl-CoA as a key indicator of their metabolic state, through distinctive protein acetylation modifications dependent on this metabolite. We offer the following conceptual model for understanding the role of this sentinel metabolite in metabolic regulation. High nucleocytosolic acetyl-CoA amounts are a signature of a 'growth' or 'fed' state and promote its utilization for lipid synthesis and histone acetylation. In contrast, under 'survival' or 'fasted' states, acetyl-CoA is preferentially directed into the mitochondria to promote mitochondrial-dependent activities such as the synthesis of ATP and ketone bodies. Fluctuations in acetyl-CoA within these subcellular compartments enable the substrate-level regulation of acetylation modifications, but also necessitate the function of sirtuin deacetylases to catalyze removal of spontaneous modifications that might be unintended. Thus, understanding the sources, fates, and consequences of acetyl-CoA as a carrier of two-carbon units has started to reveal its underappreciated but profound influence on the regulation of numerous life processes.

UR - http://www.scopus.com/inward/record.url?scp=84922987725&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922987725&partnerID=8YFLogxK

U2 - 10.1016/j.ceb.2015.02.003

DO - 10.1016/j.ceb.2015.02.003

M3 - Article

C2 - 25703630

AN - SCOPUS:84922987725

VL - 33

SP - 125

EP - 131

JO - Current Opinion in Cell Biology

JF - Current Opinion in Cell Biology

SN - 0955-0674

ER -