Journal ArticleDOI
Mitochondrial lactate oxidation complex and an adaptive role for lactate production.
TLDR
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.Abstract:
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.read more
Citations
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Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect
TL;DR: It is posited that in carcinogenesis, aberrant cell signaling due to exaggerated and continually high lactate levels yields an inappropriate positive feedback loop that increases glucose uptake, glycolysis, lactate production and release, decreases mitochondrial function and clearance and upregulates glyCOlytic enzyme and monocarboxylate transporter expression thereby supporting angiogenesis, immune escape, cell migration, metastasis and self-sufficient metabolism.
Journal ArticleDOI
Sepsis-associated hyperlactatemia
TL;DR: New evidence suggests that SAHL may actually serve to facilitate bioenergetic efficiency through an increase in lactate oxidation, which would fit the notion of an adaptive survival response that grows in intensity as disease severity increases.
Journal ArticleDOI
Monocarboxylate transporters in the brain and in cancer
Jhudit Pérez-Escuredo,Vincent F. Van Hée,Martina Sboarina,Jorge Falces,Valéry Payen,Luc Pellerin,Pierre Sonveaux +6 more
TL;DR: Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments and are part of a Special Issue entitled: Mitochondrial Channels.
Journal ArticleDOI
Structure and Organization of Mitochondrial Respiratory Complexes: A New Understanding of an Old Subject
Giorgio Lenaz,Maria Luisa Genova +1 more
TL;DR: Conditions affecting the formation of supercomplexes that, besides kinetic advantage, have a role in the stability and assembly of the individual complexes and in preventing excess oxygen radical formation are discussed.
Journal ArticleDOI
Lactate Metabolism: Historical Context, Prior Misinterpretations, And Current Understanding
Brian S. Ferguson,Matthew J. Rogatzki,Matthew L. Goodwin,Matthew L. Goodwin,Daniel A. Kane,Zachary B Rightmire,L. Bruce Gladden +6 more
TL;DR: Current understanding of La− metabolism is synthesized via an appraisal of its robust experimental history, particularly in exercise physiology, to highlight La−’s central role in metabolism and amplifies the understanding of past research.
References
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Journal ArticleDOI
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Journal ArticleDOI
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