title: Evidence for the mitochondrial lactate oxidation complex in rat neurons: demonstration of an essential component of brain lactate shuttles.
abstract: To evaluate the presence of components of a putative Intracellular Lactate Shuttle (ILS) in neurons, we attempted to determine if monocarboxylate (e.g. lactate) transporter isoforms (MCT1 and -2) and lactate dehydrogenase (LDH) are coexpressed in neuronal mitochondria of rat brains. Immunohistochemical analyses of rat brain cross-sections showed MCT1, MCT2, and LDH to colocalize with the mitochondrial inner membrane marker cytochrome oxidase (COX) in cortical, hippocampal, and thalamic neurons. Immunoblotting after immunoprecipitation (IP) of mitochondria from brain homogenates supported the histochemical observations by demonstrating that COX coprecipitated MCT1, MCT2, and LDH. Additionally, using primary cultures from rat cortex and hippocampus as well as immunohistochemistry and immunocoprecipitation techniques, we demonstrated that MCT2 and LDH are coexpressed in mitochondria of cultured neurons. These findings can be interpreted to mean that, as in skeletal muscle, neurons contain a mitochondrial lactate oxidation complex (mLOC) that has the potential to facilitate both intracellular and cell-cell lactate shuttles in brain.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, California, United States of America.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Rajaa
authors.initials: R
authors.lastname: Hussien
authors.forename: Hyung-Sook
authors.initials: HS
authors.lastname: Cho
authors.forename: Daniela
authors.initials: D
authors.lastname: Kaufer
authors.forename: George A
authors.initials: GA
authors.lastname: Brooks
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D007770:L-Lactate Dehydrogenase