Rauseo, D. | Search bioRxiv

bioRxiv2025

MPC is a facultative pyruvate / lactate exchanger

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.

cell biology↗

bioRxiv2024

Lactate-carried Mitochondrial Energy Overflow

We addressed the question of mitochondrial lactate metabolism using genetically-encoded sensors. The organelle was found to contain a dynamic lactate pool that leads to dose- and time-dependent protein lactylation. In neurons, mitochondrial lactate reported blood lactate levels with high fidelity. The exchange of lactate across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system involving the mitochondrial pyruvate carrier MPC. Assessment of electron transport chain activity and determination of lactate flux showed that mitochondria are tonic lactate producers, a phenomenon driven by energization and stimulated by hypoxia. We conclude that an overflow mechanism caps the redox level of mitochondria, while saving energy in the form of lactate. One Sentence SummaryMitochondrial lactate production

biochemistry↗