Evidence for the Mitochondrial Lactate Oxidation Complex in Rat Neurons: Demonstration of an Essential Component of Brain Lactate Shuttles
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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.
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Lactate dehydrogenase-B is present in mitochondria and is oxidatively modified by HNE in MCI hippocampus.
“Lactate dehydrogenase-B (LDH) is also present in mitochondria [67] and is oxidatively modified by HNE in MCI hippocampus [56].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [67]
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- Authors
- Hashimoto, T., Hussien, R., Cho, H.-S., Kaufer, D., & Brooks, G. A.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Brooks, George A.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-08-13
- Volume
- 3
- Issue
- 8
- Pages
- e2915
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2488371
- OpenAlex
- W1988714133
- Cited by
- 196
- References
- 43
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 8 · 2023: 14 · 2022: 9 · 2021: 10 · 2020: 14 · 2019: 7 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 5 · 2014: 11 · 2013: 17 · 2012: 13
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050459)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- lactate dehydrogenase, monocarboxylate transporters, MCT1, MCT2, neuronal mitochondria, cytochrome c oxidase, cortical neurons, hippocampal neurons, thalamic neurons
- MeSH terms
- Animals, Brain, Female, L-Lactate Dehydrogenase, Lactates, Mesencephalon, Mitochondria, Neuroglia, Neurons, Oxidation-Reduction, Rats, Wistar, Monocarboxylic Acid Transporters, Rats
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