Document Detail


Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation.
MedLine Citation:
PMID:  19254571     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondria constantly respond to changes in substrate availability and energy utilization to maintain cellular ATP supplies, and at the same time control reactive oxygen radical (ROS) production. Reversible phosphorylation of mitochondrial proteins has been proposed to play a fundamental role in metabolic homeostasis, but very little is known about the signaling pathways involved. We show here that protein kinase A (PKA) regulates ATP production by phosphorylation of mitochondrial proteins, including subunits of cytochrome c oxidase. The cyclic AMP (cAMP), which activates mitochondrial PKA, does not originate from cytoplasmic sources but is generated within mitochondria by the carbon dioxide/bicarbonate-regulated soluble adenylyl cyclase (sAC) in response to metabolically generated carbon dioxide. We demonstrate for the first time the existence of a CO(2)-HCO(3)(-)-sAC-cAMP-PKA (mito-sAC) signaling cascade wholly contained within mitochondria, which serves as a metabolic sensor modulating ATP generation and ROS production in response to nutrient availability.
Authors:
Rebeca Acin-Perez; Eric Salazar; Margarita Kamenetsky; Jochen Buck; Lonny R Levin; Giovanni Manfredi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  9     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-03     Completed Date:  2009-03-30     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  265-76     Citation Subset:  IM    
Affiliation:
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10065, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / genetics,  metabolism
Animals
Carbon Dioxide / metabolism
Cyclic AMP / metabolism*
Cyclic AMP-Dependent Protein Kinases / metabolism
HeLa Cells
Humans
Membrane Potential, Mitochondrial / physiology
Mice
Mice, Transgenic
Mitochondria / metabolism*
Mitochondrial Proteins / metabolism
Oxidation-Reduction
Oxidative Phosphorylation*
Reactive Oxygen Species / metabolism
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
K02 NS047306-01A1/NS/NINDS NIH HHS; K02 NS047306-02/NS/NINDS NIH HHS; K02 NS047306-03/NS/NINDS NIH HHS; K02 NS047306-04/NS/NINDS NIH HHS; K02 NS047306-05/NS/NINDS NIH HHS; R01 AI064842/AI/NIAID NIH HHS; R01 AI064842-04/AI/NIAID NIH HHS; R01 GM062328-06/GM/NIGMS NIH HHS; R01 GM062328-07/GM/NIGMS NIH HHS; R01 HD038722/HD/NICHD NIH HHS; R01 HD059913/HD/NICHD NIH HHS; R01 NS055255/NS/NINDS NIH HHS; R01 NS055255-03/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Mitochondrial Proteins; 0/Reactive Oxygen Species; 124-38-9/Carbon Dioxide; 60-92-4/Cyclic AMP; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 4.6.1.1/Adenylate Cyclase
Comments/Corrections

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