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Sanjuán-Pla 2005 FEBS Lett

From Bioblast
Publications in the MiPMap
Sanjuan-Pla A, Cervera AM, Apostolova N, Garcia-Bou R, Victor VM, Murphy MP, McCreath KJ (2005) A targeted antioxidant reveals the importance of mitochondrial reactive oxygen species in the hypoxic signaling of HIF-1alpha. FEBS Lett 579:2669-74.

» PMID:15862307 Open Access

Sanjuán-Pla A, Cervera AM, Apostolova N, Garcia-Bou R, Víctor VM, Murphy MP, McCreath KJ (2005) FEBS Lett

Abstract: Exposure to limiting oxygen in cells and tissues induce the stabilization and transcriptional activation of the hypoxia-inducible factor 1 alpha (HIF-1alpha) protein, a key regulator of the hypoxic response. Reactive oxygen species (ROS) generation has been implicated in the stabilization of HIF-1alpha during this response, but this is still a matter of some debate. In this study we utilize a mitochondria-targeted antioxidant, mitoubiquinone (MitoQ), and examine its effects on the hypoxic stabilization of HIF-1alpha. Our results show that under conditions of reduced oxygen (3% O(2)), MitoQ ablated the hypoxic induction of ROS generation and destabilized HIF-1alpha protein. This in turn led to an abrogation of HIF-1 transcriptional activity. Normoxic stabilization of HIF-1alpha, on the other hand, was unchanged in the presence of MitoQ suggesting that ROS were not involved. This study strongly suggests that mitochondrial ROS contribute to the hypoxic stabilization of HIF-1alpha.

Cited by

  • Komlódi T, Schmitt S, Zdrazilova L, Donnelly C, Zischka H, Gnaiger E. Oxygen dependence of hydrogen peroxide production in isolated mitochondria and permeabilized cells. MitoFit Preprints (in prep).
  • Komlódi T, Gnaiger E (2022) Discrepancy on oxygen dependence of mitochondrial ROS production - review. MitoFit Preprints 2022 (in prep).

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