Structural Mechanism of EMRE-Dependent Gating of the Human Mitochondrial Calcium Uniporter

Cell
Yan WangYouxing Jiang

Abstract

Mitochondrial calcium uptake is crucial to the regulation of eukaryotic Ca2+ homeostasis and is mediated by the mitochondrial calcium uniporter (MCU). While MCU alone can transport Ca2+ in primitive eukaryotes, metazoans require an essential single membrane-spanning auxiliary component called EMRE to form functional channels; however, the molecular mechanism of EMRE regulation remains elusive. Here, we present the cryo-EM structure of the human MCU-EMRE complex, which defines the interactions between MCU and EMRE as well as pinpoints the juxtamembrane loop of MCU and extended linker of EMRE as the crucial elements in the EMRE-dependent gating mechanism among metazoan MCUs. The structure also features the dimerization of two MCU-EMRE complexes along an interface at the N-terminal domain (NTD) of human MCU that is a hotspot for post-translational modifications. Thus, the human MCU-EMRE complex, which constitutes the minimal channel components among metazoans, provides a framework for future mechanistic studies on MCU.

References

Jan 17, 2020·Circulation Research·Tyler M Bauer, Elizabeth Murphy
Feb 26, 2020·Expert Opinion on Therapeutic Targets·Jonathan P LambertJohn W Elrod
Apr 18, 2020·Circulation Research·Jiuzhou HuoJeffery D Molkentin
Dec 11, 2019·Cell Death and Differentiation·Yohan SantinJeanne Mialet-Perez
Aug 10, 2020·Life Science Alliance·Melissa Js MacEwenYasemin Sancak
Jan 25, 2020·Cell Death & Disease·Jeanne Mialet-Perez, Angelo Parini
Aug 14, 2020·Nature Communications·Alexandros A PittisToni Gabaldón
Jul 16, 2020·ELife·Chongyuan WangStephen Barstow Long
Aug 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Horia VaisJ Kevin Foskett
Apr 1, 2020·Frontiers in Plant Science·Lorella NavazioIldikò Szabò
Oct 2, 2019·International Journal of Molecular Sciences·Nadezhda V TarasovaAndrey V Elchaninov
Feb 5, 2020·JCI Insight·Julia C LiuElizabeth Murphy
May 28, 2020·International Journal of Molecular Sciences·Megan NoblePeter B Stathopulos
Oct 3, 2020·The Journal of General Physiology·Gyorgy Csordas, Stephen Hurst
Oct 22, 2020·International Journal of Molecular Sciences·Lo Lai, Hongyu Qiu

Related Concepts

Study
Mcu-1 protein, C elegans
Neural Tube Defect, Folate-sensitive
SMDT1
EMRE protein, human
Calcium
Regulation of Biological Process
Uptake
Calcium ion
Juxtamembrane

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

© 2020 Meta ULC. All rights reserved