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Oxidative Medicine and Cellular Longevity - Volume 2017 2017, Article ID 6739236, 12 pages - https:-doi.org-10.1155-2017-6739236

Review ArticleCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA

Correspondence should be addressed to Lawrence I. Grossman

Received 6 March 2017; Accepted 9 April 2017; Published 8 June 2017

Academic Editor: Ryuichi Morishita

Copyright © 2017 Lawrence I. Grossman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The central role of energy metabolism in cellular activities is becoming widely recognized. However, there are many gaps in our knowledge of the mechanisms by which mitochondria evaluate their status and call upon the nucleus to make adjustments. Recently, a protein family consisting of twin CX9C proteins has been shown to play a role in human pathophysiology. We focus here on two family members, the isoforms CHCHD2 renamed MNRR1 and CHCHD10. The better studied isoform, MNRR1, has the unusual property of functioning in both the mitochondria and the nucleus and of having a different function in each. In the mitochondria, it functions by binding to cytochrome c oxidase COX, which stimulates respiration. Its binding to COX is promoted by tyrosine-99 phosphorylation, carried out by ABL2 kinase ARG. In the nucleus, MNRR1 binds to a novel promoter element in COX4I2 and itself, increasing transcription at 4% oxygen. We discuss mutations in both MNRR1 and CHCHD10 found in a number of chronic, mostly neurodegenerative, diseases. Finally, we propose a model of a graded response to hypoxic and oxidative stresses, mediated under different oxygen tensions by CHCHD10, MNRR1, and HIF1, which operate at intermediate and very low oxygen concentrations, respectively.





Autor: Lawrence I. Grossman, Neeraja Purandare, Rooshan Arshad, Stephanie Gladyck, Mallika Somayajulu, Maik Hüttemann, and Siddhes

Fuente: https://www.hindawi.com/



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