Petrungaro, Carmelina, Zimmermann, Katharina M., Kuettner, Victoria, Fischer, Manuel, Dengjel, Joern ORCID: 0000-0002-9453-4614, Bogeski, Ivan ORCID: 0000-0001-9879-7174 and Riemer, Jan (2015). The Ca2+-Dependent Release of the Mia40-Induced MICU1-MICU2 Dimer from MCU Regulates Mitochondrial Ca2+ Uptake. Cell Metab., 22 (4). S. 721 - 734. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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Abstract

The essential oxidoreductase Mia40/CHCHD4 mediates disulfide bond formation and protein folding in the mitochondrial intermembrane space. Here, we investigated the interactome of Mia40 thereby revealing linksbetween thiol-oxidation and apoptosis, energy metabolism, and Ca2+ signaling. Among the interaction partners of Mia40 is MICU1-the regulator of the mitochondrial Ca2+ uniporter (MCU), which transfers Ca2+ across the inner membrane. We examined the biogenesis of MICU1 and find that Mia40 introduces an intermolecular disulfide bond that links MICU1 and its inhibitory paralog MICU2 in a heterodimer. Absence of this disulfide bond results in increased receptor-induced mitochondrial Ca2+ uptake. In the presence of the disulfide bond, MICU1-MICU2 heterodimer binding to MCU is controlled by Ca2+ levels: the dimer associates with MCU at lowlevels of Ca2+ and dissociates upon high Ca2+ concentrations. Our findings support a model in which mitochondrial Ca2+ uptake is regulated by a Ca2+ dependent remodeling of the uniporter complex.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Petrungaro, CarmelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmermann, Katharina M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuettner, VictoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dengjel, JoernUNSPECIFIEDorcid.org/0000-0002-9453-4614UNSPECIFIED
Bogeski, IvanUNSPECIFIEDorcid.org/0000-0001-9879-7174UNSPECIFIED
Riemer, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-390007
DOI: 10.1016/j.cmet.2015.08.019
Journal or Publication Title: Cell Metab.
Volume: 22
Number: 4
Page Range: S. 721 - 734
Date: 2015
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INTERMEMBRANE SPACE; CALCIUM UNIPORTER; ELECTRON-TRANSFER; YEAST MITOCHONDRIA; INNER MEMBRANE; PROTEIN IMPORT; MIA40; MICU1; CELLS; GLUTATHIONEMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/39000

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