Lactate metabolism is associated with mammalian mitochondria
Open accessAbstract
It is well established that lactate secreted by fermenting cells can be oxidized or used as a gluconeogenic substrate by other cells and tissues. It is generally assumed, however, that within the fermenting cell itself, lactate is produced to replenish NAD+ and then is secreted. Here we explore the possibility that cytosolic lactate is metabolized by the mitochondria of fermenting mammalian cells. We found that fermenting HeLa and H460 cells utilize exogenous lactate carbon to synthesize a large percentage of their lipids. Using high-resolution mass spectrometry, we found that both 13 C and 2-2 H labels from enriched lactate enter the mitochondria. The lactate dehydrogenase (LDH) inhibitor oxamate decreased respiration of isolated mitochondria incubated in lactate, but not of isolated mitochondria incubated in pyruvate. Additionally, transmission electron microscopy (TEM) showed that LDHB localizes to the mitochondria. Taken together, our results demonstrate a link between lactate metabolism and the mitochondria of fermenting mammalian cells.
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Mitochondrial import and catabolism of lactate would prevent the buildup of cytosolic NADH while allowing for the mitochondrial capture of both carbon and reducing equivalents.
“Mitochondrial import and catabolism of lactate would prevent the buildup of cytosolic NADH while allowing for the mitochondrial capture of both carbon and reducing equivalents (61).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [61]
One study found that LDH can localize to the mitochondria, raising the possibility that lactate can be directly imported into the mitochondria for further oxidation.
“Suggestively, one study found that LDH can localize to the mitochondria, raising the possibility that lactate can be directly imported into the mitochondria for further oxidation (61).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [61]
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References 35 · Cited by 326
- Authors
- Chen, Y.-J., Mahieu, N. G., Huang, X., Singh, M., Crawford, P. A., Johnson, S. L., Gross, R. W., Schaefer, J., & Patti, G. J.
- Affiliations
- Washington University in St. Louis (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Patti, Gary J
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2016-09-12
- Volume
- 12
- Issue
- 11
- Pages
- 937-943
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC5069139
- OpenAlex
- W2519338564
- Cited by
- 326
- References
- 35
- Citations by year
- 2026: 26 · 2025: 45 · 2024: 35 · 2023: 38 · 2022: 48 · 2021: 33 · 2020: 35 · 2019: 22 · 2018: 28 · 2017: 15
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL118639)
- National Cancer Institute (R21CA191097)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK091538)
- National Institute of Environmental Health Sciences (R01ES022181)
- National Institute of Biomedical Imaging and Bioengineering (R01EB002058)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- lactate metabolism, lactate dehydrogenase, pyruvate production, NAD+ regeneration, lactate oxidation, lipogenesis, oxamate, mitochondrial respiration, HeLa cells, H460 cells
- MeSH terms
- HeLa Cells, Humans, Mitochondria, Molecular Structure, Lactic Acid, Cell Line, Tumor
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