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MICU1 and MICU2 Finely Tune the Mitochondrial Ca2+ Uniporter by Exerting Opposite Effects on MCU Activity

Open access
Patron, Maria, Checchetto, Vanessa, Raffaello, Anna, Teardo, Enrico, Vecellio Reane, Denis, Mantoan, Maura, Granatiero, Veronica, Szabò, Ildikò, De Stefani, Diego, Rizzuto, Rosario·2014·Molecular Cell

Abstract

Mitochondrial calcium accumulation was recently shown to depend on a complex composed of an inner-membrane channel (MCU and MCUb) and regulatory subunits (MICU1, MCUR1, and EMRE). A fundamental property of MCU is low activity at resting cytosolic Ca(2+) concentrations, preventing deleterious Ca(2+) cycling and organelle overload. Here we demonstrate that these properties are ensured by a regulatory heterodimer composed of two proteins with opposite effects, MICU1 and MICU2, which, both in purified lipid bilayers and in intact cells, stimulate and inhibit MCU activity, respectively. Both MICU1 and MICU2 are regulated by calcium through their EF-hand domains, thus accounting for the sigmoidal response of MCU to [Ca(2+)] in situ and allowing tight physiological control. At low [Ca(2+)], the dominant effect of MICU2 largely shuts down MCU activity; at higher [Ca(2+)], the stimulatory effect of MICU1 allows the prompt response of mitochondria to Ca(2+) signals generated in the cytoplasm.

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Crossref · 10.1016/j.molcel.2014.01.013

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Metadata

Authors
Patron, M., Checchetto, V., Raffaello, A., Teardo, E., Vecellio Reane, D., Mantoan, M., Granatiero, V., Szabò, I., De Stefani, D., & Rizzuto, R.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2014-03
Volume
53
Issue
5
Pages
726-737
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2142903428
Cited by
517
References
6
FWCI
16.79
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: MICU1 and MICU2 Finely Tune the Mitochondrial Ca2+ Uniporter by Exerting Opposite Effects on MCU Activity. https://app.cochat.ai/papers/10.1016/j.molcel.2014.01.013
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Patron, M., Checchetto, V., Raffaello, A., Teardo, E., Vecellio Reane, D., Mantoan, M., Granatiero, V., Szabò, I., De Stefani, D., & Rizzuto, R. (2014). MICU1 and MICU2 Finely Tune the Mitochondrial Ca2+ Uniporter by Exerting Opposite Effects on MCU Activity. Molecular Cell. https://doi.org/10.1016/j.molcel.2014.01.013

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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