TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy
| Autor: | Li Zhang, Felicia Dietsche, Bruno Seitaj, Liliana Rojas-Charry, Nadina Latchman, Dhanendra Tomar, Rob CI Wüst, Alexander Nickel, Katrin BM Frauenknecht, Benedikt Schoser, Sven Schumann, Michael J Schmeisser, Johannes vom Berg, Thorsten Buch, Stefanie Finger, Philip Wenzel, Christoph Maack, John W Elrod, Jan B Parys, Geert Bultynck, Axel Methner |
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| Přispěvatelé: | University of Zurich, Methner, Axel, Physiology, AMS - Ageing & Vitality, AMS - Musculoskeletal Health |
| Rok vydání: | 2022 |
| Předmět: |
Ecology
Health Toxicology and Mutagenesis 610 Medizin 610 Medicine & health Apoptosis Plant Science Genetics and Molecular Biology (miscellaneous) Biochemistry Genetics and Molecular Biology (miscellaneous) 1301 Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Mitochondrial Membrane Transport Proteins Mice Muscular Diseases Health 610 Medical sciences 1110 Plant Science 2307 Health Toxicology and Mutagenesis 570 Life sciences biology 590 Animals (Zoology) Animals Homeostasis 10239 Institute of Laboratory Animal Science Toxicology and Mutagenesis Calcium 2303 Ecology |
| Zdroj: | Life science alliance, 5(10):e202201478, 1-15. Rockefeller University Press Zhang, L, Dietsche, F, Seitaj, B, Rojas-Charry, L, Latchman, N, Tomar, D, Wüst, R C, Nickel, A, Frauenknecht, K B, Schoser, B, Schumann, S, Schmeisser, M J, Vom Berg, J, Buch, T, Finger, S, Wenzel, P, Maack, C, Elrod, J W, Parys, J B, Bultynck, G & Methner, A 2022, ' TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy ', Life science alliance, vol. 5, no. 10, e202201478, pp. 1-15 . https://doi.org/10.26508/lsa.202201478 |
| ISSN: | 2575-1077 |
| Popis: | 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. ispartof: LIFE SCIENCE ALLIANCE vol:5 issue:10 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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