Loss of UCP2 Attenuates Mitochondrial Dysfunction without Altering ROS Production and Uncoupling Activity

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Mitochondria produce the majority of the energy needed for numerous cell functions through oxidative phosphorylation. However, this comes with the cost in the form of potentially harmful reactive oxygen species (ROS) that could damage all kinds of biological macromolecules. Changes in mitochondrial membrane potential through mild uncoupling could alter ROS production in the cell (“uncoupling to survive”). Mitochondrial uncoupling proteins (UCPs) are believed to play a central role in this process. We detected increased amounts of UCP2 in mtDNA mutator mice, a model for premature aging. Depletion of UCP2 in mtDNA mutator mice led to further shortening of the lifespan with earlier signs of mitochondrial cardiomyopathy accompanied with high systemic lactic acidosis, often used as a marker of mitochondrial diseases. Remarkably, our results demonstrate that the presence of UCP2 wields beneficial effect on respiratory deficient mitochondria without affecting ROS production or uncoupling. Instead, UCP2 protein seems to mediate a valuable upregulation of fatty acid metabolism detected in mtDNA mutator hearts. Our results provide a novel mechanism of adaptation of mitochondria to respiratory deficiency mediated by UCP2 that clearly argues against the “uncoupling to survive” theory.

Vyšlo v časopise: Loss of UCP2 Attenuates Mitochondrial Dysfunction without Altering ROS Production and Uncoupling Activity. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004385
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004385

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