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Evidence for the Mitochondrial Lactate Oxidation Complex in Rat Neurons: Demonstration of an Essential Component of Brain Lactate Shuttles
Open accessAbstract
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 (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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Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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