دورية أكاديمية
TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy
| العنوان: | TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy |
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| المؤلفون: | Zhang, Li, Dietsche, Felicia, Seitaj, Bruno, Rojas-Charry, Liliana, Latchman, Nadina, Tomar, Dhanendra, Wüst, Rob C I, Nickel, Alexander, Frauenknecht, Katrin B M, Schoser, Benedikt, Schumann, Sven, Schmeisser, Michael J, vom Berg, Johannes, Buch, Thorsten, Finger, Stefanie, Wenzel, Philip, Maack, Christoph, Elrod, John W, Parys, Jan B, Bultynck, Geert, Methner, Axel |
| المصدر: | Zhang, Li; Dietsche, Felicia; Seitaj, Bruno; Rojas-Charry, Liliana; Latchman, Nadina; Tomar, Dhanendra; Wüst, Rob C I; Nickel, Alexander; Frauenknecht, Katrin B M; Schoser, Benedikt; Schumann, Sven; Schmeisser, Michael J; vom Berg, Johannes; Buch, Thorsten; Finger, Stefanie; Wenzel, Philip; Maack, Christoph; Elrod, John W; Parys, Jan B; Bultynck, Geert; Methner, Axel (2022). TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy. Life Science Alliance, 5(10):e202201478. |
| بيانات النشر: | Life Science Alliance |
| سنة النشر: | 2022 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Institute of Laboratory Animal Science, 570 Life sciences, biology, 590 Animals (Zoology), 610 Medicine & health, Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology |
| الوصف: | Ion fluxes across the inner mitochondrial membrane control mitochondrial volume, energy production, and apoptosis. TMBIM5, a highly conserved protein with homology to putative pH-dependent ion channels, is involved in the maintenance of mitochondrial cristae architecture, ATP production, and apoptosis. Here, we demonstrate that overexpressed TMBIM5 can mediate mitochondrial calcium uptake. Under steady-state conditions, loss of TMBIM5 results in increased potassium and reduced proton levels in the mitochondrial matrix caused by attenuated exchange of these ions. To identify the in vivo consequences of TMBIM5 dysfunction, we generated mice carrying a mutation in the channel pore. These mutant mice display increased embryonic or perinatal lethality and a skeletal myopathy which strongly correlates with tissue-specific disruption of cristae architecture, early opening of the mitochondrial permeability transition pore, reduced calcium uptake capability, and mitochondrial swelling. Our results demonstrate that TMBIM5 is an essential and important part of the mitochondrial ion transport system machinery with particular importance for embryonic development and muscle function. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2575-1077 |
| العلاقة: | https://www.zora.uzh.ch/id/eprint/219055/1/e202201478.full.pdfTest; info:pmid/35715207; urn:issn:2575-1077 |
| DOI: | 10.5167/uzh-219055 |
| DOI: | 10.26508/lsa.202201478 |
| الإتاحة: | https://doi.org/10.5167/uzh-21905510.26508/lsa.202201478Test https://www.zora.uzh.ch/id/eprint/219055Test/ https://www.zora.uzh.ch/id/eprint/219055/1/e202201478.full.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.3138A04A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 25751077 |
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| DOI: | 10.5167/uzh-219055 |