Venue: Centre Broca
Felipe Barros
Center for Scientific Studies (CECs) & Universidad San Sebastian (Valdivia, Chile)
https://researchers.uss.cl/es/persons/luis-felipe-barros-olmedo
Invited by Ignacio Fernandez-Moncada and Giovanni Marsicano
Title
Lactate-carried Mitochondrial Energy Overflow
Abstract
Lactate is a cytosolic metabolite and an extracellular signal that transfers carbons, energy and information between cells and between organs. This EMBO Global lecture will present evidence of an additional role for lactate, which involves mitochondria.
Using genetically-encoded fluorescent probes we observed that the mitochondrial matrix of every cell tested contains a dynamic lactate pool. In neurons, mitochondrial lactate reported blood lactate fluctuations with high fidelity, demonstrating high permeability of all membrane barriers interposed between plasma and the matrix. Passage across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system. Surprisingly, pharmacological and genetic approaches revealed that this lactate permeability involves the mitochondrial pyruvate carrier MPC, a transporter hitherto deemed specific for pyruvate.
What is the (patho)physiological role of mitochondrial lactate? Determination of fluxes, redox status and energization showed that mitochondria do not consume lactate. Rather, they produce it. Strikingly, lactate production was stimulated within seconds of exposure to hypoxia.
We propose that mitochondria produce lactate to modulate reductive stress and the ensuing production of reactive oxygen species, a role reminiscent of that of uncoupling proteins. There are however some distinctions. Mitochondrial uncoupling consumes oxygen and discards the chemical energy of substrates irreversibly as heat. In contrast, the present overflow mechanism spares oxygen and saves the energy in a form that can be recycled.
Rauseo et al., bioRxiv 2024. doi: https://doi.org/10.1101/2024.07.19.604361