Lactate activates the mitochondrial electron transport chain independently of its metabolism, 2023, Xin Cai et al

Highlights

• Lactate is a mitochondrial messenger that shifts ATP production to the mitochondria
• It activates the electron transport chain (ETC) without being metabolized
• Lactate-induced ETC activation increases pyruvate oxidation and lactate utilization
• Mitochondrial ETC can sense the availability of lactate as a nutrient

Summary
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.

https://www.cell.com/molecular-cell/fulltext/S1097-2765(23)00800-6

 

Another "everybody knows" bit of knowledge shown to be wrong. Is understanding of ME being held up by a similar incorrect "everybody knows"?