Lactate activates the mitochondrial electron transport chain independently of its metabolism Journal Article
| Authors: | Cai, X.; Ng, C. P.; Jones, O.; Fung, T. S.; Ryu, K. W.; Li, D.; Thompson, C. B. |
| Article Title: | Lactate activates the mitochondrial electron transport chain independently of its metabolism |
| Abstract: | Lactate has long been considered a cellular waste product. However, we found that as extracellular lactate accumulates, it also enters the mitochondrial matrix and stimulates mitochondrial electron transport chain (ETC) activity. The resulting increase in mitochondrial ATP synthesis suppresses glycolysis and increases the utilization of pyruvate and/or alternative respiratory substrates. The ability of lactate to increase oxidative phosphorylation does not depend on its metabolism. Both L- and D-lactate are effective at enhancing ETC activity and suppressing glycolysis. Furthermore, the selective induction of mitochondrial oxidative phosphorylation by unmetabolized D-lactate reversibly suppressed aerobic glycolysis in both cancer cell lines and proliferating primary cells in an ATP-dependent manner and enabled cell growth on respiratory-dependent bioenergetic substrates. In primary T cells, D-lactate enhanced cell proliferation and effector function. Together, these findings demonstrate that lactate is a critical regulator of the ability of mitochondrial oxidative phosphorylation to suppress glucose fermentation. © 2023 Elsevier Inc. |
| Keywords: | metabolism; physiology; adenosine triphosphate; mitochondria; energy metabolism; glycolysis; oxidative phosphorylation; lactic acid; electron transport; lactate; electron transport chain; tca cycle |
| Journal Title: | Molecular Cell |
| Volume: | 83 |
| Issue: | 21 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2023-11-02 |
| Start Page: | 3904 |
| End Page: | 3920.e7 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2023.09.034 |
| PUBMED: | 37879334 |
| PROVIDER: | scopus |
| PMCID: | PMC10752619 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Craig Thompson -- Source: Scopus |
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