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Oxygen Sensing and HIF-1 Activation Does Not Require an Active Mitochondrial Respiratory Chain Electron-transfer Pathway
Journal article   Open access   Peer reviewed

Oxygen Sensing and HIF-1 Activation Does Not Require an Active Mitochondrial Respiratory Chain Electron-transfer Pathway

Vickram Srinivas, Irene Leshchinsky, Nianli Sang, Michael P King, Alex Minchenko and Jaime Caro
The Journal of biological chemistry, v 276(25), pp 21995-21998
22 Jun 2001
PMID: 11342528
url
https://doi.org/10.1074/jbc.C100177200View
Published, Version of Record (VoR) Open

Abstract

Hypoxia induces the stabilization and transcriptional activation of the hypoxia-inducible factor 1 α (HIF-1 α ) protein, the regulatory member of the HIF-1 complex. The molecular mechanisms that are responsible for oxygen sensing and the downstream pathways utilized by the hypoxic signal are still poorly understood. One hypothesis for oxygen sensing has postulated that reactive oxygen species generated at mitochondrial complex III are the initiators of the hypoxic signal. Here we find that mitochondrial DNA-less ( ρ o ) cells have a normal response to hypoxia, measured at the level of HIF-1 α protein stabilization, nuclear translocation, and its transcriptional activation activity. Furthermore, overexpression of catalase, either in the mitochondria or in the cytosol, fails to modify the hypoxia response indicating that hydrogen peroxide is not a signaling molecule in the hypoxic signaling cascade that culminates with HIF-1 activation.

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Web of Science research areas
Biochemistry & Molecular Biology
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