The human mitochondrial DNA depletion syndrome gene MPV17 encodes a non-selective channel that modulates membrane potential
|Author:||Antonenkov, Vasily D.1; Isomursu, Antti1; Mennerich, Daniela1;|
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
|Online Access:||PDF Full Text (PDF, 3.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201703152193
American Society for Biochemistry and Molecular Biology,
|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.
Journal of biological chemistry
|Pages:||13840 - 13861|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was supported by grants from the Academy of Finland, the Sigrid Juselius Foundation, and Biocenter Oulu.
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in this repository with the kind permission of the publisher.