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TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy
Zhang, Li Dietsche, Felicia Seitaj, Bruno Rojas-Charry, Liliana Latchman, Nadina Wüst, Rob C.I. Nickel, Alexander Frauenknecht, Katrin B. M. Schoser, Benedikt
Zhang, Li
Dietsche, Felicia
Seitaj, Bruno
Rojas-Charry, Liliana
Latchman, Nadina
Wüst, Rob C.I.
Nickel, Alexander
Frauenknecht, Katrin B. M.
Schoser, Benedikt
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Journal article
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2022-06-17
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Cardiovascular Sciences
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http://dx.doi.org/10.26508/lsa.202201478
Abstract
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.
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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 Life Science Alliance Jun 2022, 5 (10) e202201478; DOI: 10.26508/lsa.202201478
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Life Science Alliance, Vol. 5, No. 10
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