Journal article
Knockout of cyclophilin D in Ppif(-/-) mice increases stability of brain mitochondria against Ca2+ stress
Archives of biochemistry and biophysics, v 579, pp 40-46
01 Aug 2015
PMID: 26032335
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The mitochondrial peptidyl prolyl isomerase cyclophilin D (CypD) activates permeability transition (PT). To study the role of CypD in this process we compared the functions of brain mitochondria isolated from wild type (BMWT) and CypD knockout (Ppif(-/-)) mice (BMKO) with and without CypD inhibitor Cyclosporin A (CsA) under normal and Ca2+ stress conditions. Our data demonstrate that BMKO are characterized by higher rates of glutamate/malate-dependent oxidative phosphorylation, higher membrane potential and higher resistance to detrimental Ca2+ effects than BMWT. Under the elevated Ca2+ and correspondingly decreased membrane potential the dose response in BMKO shifts to higher Ca2+ concentrations as compared to BMWT. However, significantly high Ca2+ levels result in complete loss of membrane potential in BMKO, too. CsA diminishes the loss of membrane potential in BMWT but has no protecting effect in BMKO. The results are in line with the assumption that PT is regulated by CypD under the control of matrix Ca2+. Due to missing of CypD the BMKO can favor PT only at high Ca2+ concentrations. It is concluded that CypD sensitizes the brain mitochondria to PT, and its inhibition by CsA or CypD absence improves the complex I-related mitochondrial function and increases mitochondria stability against Ca2+ stress. (C) 2015 Published by Elsevier Inc.
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Details
- Title
- Knockout of cyclophilin D in Ppif(-/-) mice increases stability of brain mitochondria against Ca2+ stress
- Creators
- T. Gainutdinov - Department of Neurology, Otto-von-Guericke-University, Magdeburg D-39120, Germany; Institute of Ecology and Use of Mineral Resources, Academy of Sciences of Tatarstan, Kazan 420087, Russian Federation.J. D. Molkentin - Cincinnati Children's Hospital Medical CenterD. Siemen - Otto-von-Guericke University MagdeburgM. Ziemer - Otto-von-Guericke University MagdeburgG. Debska-Vielhaber - Otto-von-Guericke University MagdeburgS. Vielhaber - Otto-von-Guericke University MagdeburgZ. Gizatullina - Leibniz Institute for NeurobiologyZ. Orynbayeva - Drexel UniversityF. N. Gellerich - Otto-von-Guericke University Magdeburg
- Publication Details
- Archives of biochemistry and biophysics, v 579, pp 40-46
- Publisher
- Elsevier
- Number of pages
- 7
- Grant note
- Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE) Drexel University Professional Enrichment and Growth Grant
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000358552000006
- Scopus ID
- 2-s2.0-84935890121
- Other Identifier
- 991019167411604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics