University of Oulu

Antonenkov, Vasily D.; Isomursu, Antti; Mennerich, Daniela; Vapola, Miia H.; Weiher, Hans; Kietzmann, Thomas; Hiltunen, J. Kalervo

The human mitochondrial DNA depletion syndrome gene MPV17 encodes a non-selective channel that modulates membrane potential

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Author: Antonenkov, Vasily D.1; Isomursu, Antti1; Mennerich, Daniela1;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, P.O. Box 3000, FI-90014 Oulu, Finland
2Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.7 MB)
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Language: English
Published: American Society for Biochemistry and Molecular Biology, 2015
Publish Date: 2017-03-15


The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel’s selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17−/− mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions.

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Series: Journal of biological chemistry
ISSN: 0021-9258
ISSN-E: 1067-8816
ISSN-L: 0021-9258
Volume: 290
Issue: 22
Pages: 13840 - 13861
DOI: 10.1074/jbc.M114.608083
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by grants from the Academy of Finland, the Sigrid Juselius Foundation, and Biocenter Oulu.
Copyright information: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in this repository with the kind permission of the publisher.