Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Petrungaro, Carmelina UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmermann, Katharina M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuettner, Victoria UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Dengjel, Joern UNSPECIFIED orcid.org/0000-0002-9453-4614 UNSPECIFIED Bogeski, Ivan UNSPECIFIED orcid.org/0000-0001-9879-7174 UNSPECIFIED Riemer, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language INTERMEMBRANE SPACE; CALCIUM UNIPORTER; ELECTRON-TRANSFER; YEAST MITOCHONDRIA; INNER MEMBRANE; PROTEIN IMPORT; MIA40; MICU1; CELLS; GLUTATHIONE Multiple languages Cell Biology; Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/39000