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Lactate-carried Mitochondrial Energy Overflow.

Daniela RauseoYasna Contreras-BaezaHugo FaurandNataly CárcamoRaibel SuárezAlexandra von Faber-CastellFranco SilvaValentina Mora-GonzálezMatthias T WyssFelipe Baeza-LehnertIván RuminotCarlos Alvarez-NavarroAlejandro San MartínBruno WeberPamela Y SandovalLuis Felipe Barros
Published in: bioRxiv : the preprint server for biology (2024)
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.
Keyphrases
  • oxidative stress
  • cell death
  • spinal cord
  • endothelial cells
  • mass spectrometry
  • simultaneous determination