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Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2

Authors :
Chongyuan Wang
Agata Jacewicz
Bryce D Delgado
Rozbeh Baradaran
Stephen Barstow Long
Source :
eLife, Vol 9 (2020)
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

The mitochondrial calcium uniporter is a Ca2+-gated ion channel complex that controls mitochondrial Ca2+ entry and regulates cell metabolism. MCU and EMRE form the channel while Ca2+-dependent regulation is conferred by MICU1 and MICU2 through an enigmatic process. We present a cryo-EM structure of an MCU-EMRE-MICU1-MICU2 holocomplex comprising MCU and EMRE subunits from the beetle Tribolium castaneum in complex with a human MICU1-MICU2 heterodimer at 3.3 Å resolution. With analogy to how neuronal channels are blocked by protein toxins, a uniporter interaction domain on MICU1 binds to a channel receptor site comprising MCU and EMRE subunits to inhibit ion flow under resting Ca2+ conditions. A Ca2+-bound structure of MICU1-MICU2 at 3.1 Å resolution indicates how Ca2+-dependent changes enable dynamic response to cytosolic Ca2+ signals.

Details

Language :
English
ISSN :
2050084X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.babbf9f640f54b3e8fb3f9f3f6888c17
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.59991