Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gottschalk, B; Koshenov, Z; Waldeck-Weiermair, M; Radulović, S; Oflaz, FE; Hirtl, M; Bachkoenig, OA; Leitinger, G; Malli, R; Graier, WF.
MICU1 controls spatial membrane potential gradients and guides Ca2+ fluxes within mitochondrial substructures.
Commun Biol. 2022; 5(1): 649
Doi: 10.1038/s42003-022-03606-3
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- Führende Autor*innen der Med Uni Graz
- Gottschalk Benjamin
- Graier Wolfgang
- Co-Autor*innen der Med Uni Graz
- Bachkönig Olaf Arne Georg
- Hirtl Martin
- Koshenov Zhanat
- Leitinger Gerd
- Malli Roland
- Oflaz Furkan Enes
- Radulovic Snjezana
- Waldeck-Weiermair Markus
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- Abstract:
- Mitochondrial ultrastructure represents a pinnacle of form and function, with the inner mitochondrial membrane (IMM) forming isolated pockets of cristae membrane (CM), separated from the inner-boundary membrane (IBM) by cristae junctions (CJ). Applying structured illumination and electron microscopy, a novel and fundamental function of MICU1 in mediating Ca2+ control over spatial membrane potential gradients (SMPGs) between CM and IMS was identified. We unveiled alterations of SMPGs by transient CJ openings when Ca2+ binds to MICU1 resulting in spatial cristae depolarization. This Ca2+/MICU1-mediated plasticity of the CJ further provides the mechanistic bedrock of the biphasic mitochondrial Ca2+ uptake kinetics via the mitochondrial Ca2+ uniporter (MCU) during intracellular Ca2+ release: Initially, high Ca2+ opens CJ via Ca2+/MICU1 and allows instant Ca2+ uptake across the CM through constantly active MCU. Second, MCU disseminates into the IBM, thus establishing Ca2+ uptake across the IBM that circumvents the CM. Under the condition of MICU1 methylation by PRMT1 in aging or cancer, UCP2 that binds to methylated MICU1 destabilizes CJ, disrupts SMPGs, and facilitates fast Ca2+ uptake via the CM.