| Mitochondrial lactate oxidation complex and an adaptive role for lactate production. | |
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MedLine Citation:
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PMID: 18379211 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The intracellular lactate shuttle (ILS) hypothesis holds that lactate produced as the result of glycolysis and glycogenolysis in the cytosol is balanced by oxidative removal in mitochondria of the same cell. Also, the ILS is a necessary component of the previously described cell-cell lactate shuttle (CCLS), because lactate supplied from the interstitium and vasculature can be taken up and used in highly oxidative cells (red skeletal and cardiac myocytes, hepatocytes, and neurons). This ILS emphasizes the role of mitochondrial redox in creating the proton and lactate anion concentration gradients necessary for the oxidative disposal of lactate in the mitochondrial reticulum during exercise and other conditions. The hypothesis was initially supported by direct measurement of lactate oxidation in isolated mitochondria as well as findings of the existence of mitochondrial monocarboxylate transporters (mMCT) and lactate dehydrogenase (mLDH). Subsequently, the presence of a mitochondrial lactate oxidation complex (composed of mMCT1, CD147 (basigin), mLDH, and cytochrome oxidase (COX)) was discovered, which lends support to the presence of the ILS. Most recently, efforts have been made to evaluate the role of lactate as a cell-signaling molecule (i.e., a "lactormone") that is involved in the adaptive response to exercise. Lactate is capable of upregulating MCT1 and COX gene and protein expression. Current findings allow us to understand how lactate production during exercise represents a physiological signal for the activation of a vast transcription network affecting MCT1 protein expression and mitochondrial biogenesis, thereby explaining how training increases the capacity for lactate clearance via oxidation. |
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Authors:
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Takeshi Hashimoto; George A Brooks |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Medicine and science in sports and exercise Volume: 40 ISSN: 0195-9131 ISO Abbreviation: Med Sci Sports Exerc Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-04-01 Completed Date: 2008-05-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8005433 Medline TA: Med Sci Sports Exerc Country: United States |
Other Details:
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Languages: eng Pagination: 486-94 Citation Subset: IM; S |
Affiliation:
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Department of Integrative Biology, University of California, Berkeley, CA 94720-3140, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acidosis, Lactic
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metabolism* Adaptation, Physiological Antigens, CD147 / metabolism Electron Transport Complex IV / metabolism Humans L-Lactate Dehydrogenase / metabolism Lactic Acid / metabolism* Mitochondria, Muscle / enzymology, metabolism* Monocarboxylic Acid Transporters / metabolism Muscle, Skeletal / enzymology, metabolism, physiology Reactive Oxygen Species / metabolism United States |
| Grant Support | |
ID/Acronym/Agency:
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R01 AR050459/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Monocarboxylic Acid Transporters; 0/Reactive Oxygen Species; 136894-56-9/Antigens, CD147; 50-21-5/Lactic Acid; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.9.3.1/Electron Transport Complex IV |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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