Authors:	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. Berg, Johannes vom Buch, Thorsten Finger, Stefanie Wenzel, Philip Maack, Christoph Elrod, John W. Parys, Jan B. Bultynck, Geert Methner, Axel
Title:	TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy
Online publication date:	13-Jan-2023
Year of first publication:	2022
Language:	english
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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8568
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Life science alliance 5 10
Pages or article number:	e202201478
Publisher:	EMBO Press
Publisher place:	Heidelberg
Issue date:	2022
ISSN:	2575-1077
Publisher DOI:	10.26508/lsa.202201478
Appears in collections:	DFG-491381577-G