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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Zhang, L; Gottschalk, B; Dietsche, F; Bitar, S; Bueno, D; Rojas-Charry, L; Kumari, A; Garg, V; Graier, WF; Methner, A.
Interaction of the mitochondrial calcium/proton exchanger TMBIM5 with MICU1.
Commun Biol. 2025; 8(1):1348 Doi: 10.1038/s42003-025-08839-6 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Gottschalk Benjamin
Graier Wolfgang
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Abstract:
Ion transport within mitochondria influences their structure, energy production, and cell death regulation. TMBIM5, a conserved calcium/proton exchanger in the inner mitochondrial membrane, contributes to mitochondrial structure, ATP synthesis, and apoptosis regulation. The relationship of TMBIM5 with the mitochondrial calcium uniporter complex formed by MCU, MICU1-3, and EMRE remains undefined. We generated Tmbim5-deficient Drosophila that exhibit disrupted cristae architecture, premature mitochondrial permeability transition pore opening, reduced calcium uptake, and mitochondrial swelling - resulting in impaired mobility and shortened lifespan. Crossing these with flies lacking mitochondrial calcium uniporter complex proteins was generally detrimental, but partial MICU1 depletion ameliorated the Tmbim5-deficiency phenotype. In human cells, MICU1 rescues morphological defects in TMBIM5-knockout mitochondria, while TMBIM5 overexpression exacerbates size reduction in MICU1-knockout mitochondria. Both proteins demonstrated opposing effects on submitochondrial localization and coexisted in the same macromolecular complex. Our findings establish a functional interplay between TMBIM5 and MICU1 in maintaining mitochondrial integrity, with implications for understanding calcium homeostasis mechanisms.
Find related publications in this database (using NLM MeSH Indexing)
Animals - administration & dosage
Mitochondrial Membrane Transport Proteins - metabolism, genetics
Calcium-Binding Proteins - metabolism, genetics
Humans - administration & dosage
Mitochondria - metabolism
Calcium - metabolism
Cation Transport Proteins - metabolism, genetics
Drosophila Proteins - metabolism, genetics
Calcium Channels - metabolism, genetics
Membrane Proteins - metabolism, genetics
Drosophila melanogaster - metabolism, genetics

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