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MPC is a facultative pyruvate / lactate exchanger

Carcamo-Lemus, N.; Rauseo, D.; San Martin, A.; Lagos, C. F.; Barros, L. F.; Sandoval, P. Y.

2025-12-01 cell biology
10.1101/2025.11.29.691055 bioRxiv
Show abstract

The mitochondrial uptake of pyruvate is mediated by the MPC. In the present study, we investigated the functional properties of the carrier using genetically encoded fluorescent sensors. Mitochondrial lactate efflux was inhibited by >80% by both pharmacological and genetic MPC ablation. MPC-dependent pyruvate influx accelerated the efflux of lactate, a fingerprint of shared transport. The non-metabolized pyruvate analog oxamate, which was found to enter mitochondria solely through the MPC, was also able to trans-accelerate lactate. Reportedly, mitochondria can produce lactate under reductive stress; our findings indicate that the MPC participates in this energy/redox venting by exchanging pyruvate by lactate.

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