Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex.

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dc.contributor.author Tsai, Ming-Feng
dc.contributor.author Phillips, Charles B
dc.contributor.author Ranaghan, Matthew
dc.contributor.author Tsai, Chen-Wei
dc.contributor.author Wu, Yujiao
dc.contributor.author Willliams, Carole
dc.contributor.author Miller, Christopher
dc.date.accessioned 2019-01-17T19:21:54Z
dc.date.available 2019-01-17T19:21:54Z
dc.date.issued 2016
dc.identifier.issn 2050-084X
dc.identifier.other PMC4892889
dc.identifier.uri https://hdl.handle.net/10192/36103
dc.description.abstract Mitochondrial Ca(2+) uptake, a process crucial for bioenergetics and Ca(2+) signaling, is catalyzed by the mitochondrial calcium uniporter. The uniporter is a multi-subunit Ca(2+)-activated Ca(2+) channel, with the Ca(2+) pore formed by the MCU protein and Ca(2+)-dependent activation mediated by MICU subunits. Recently, a mitochondrial inner membrane protein EMRE was identified as a uniporter subunit absolutely required for Ca(2+) permeation. However, the molecular mechanism and regulatory purpose of EMRE remain largely unexplored. Here, we determine the transmembrane orientation of EMRE, and show that its known MCU-activating function is mediated by the interaction of transmembrane helices from both proteins. We also reveal a second function of EMRE: to maintain tight MICU regulation of the MCU pore, a role that requires EMRE to bind MICU1 using its conserved C-terminal polyaspartate tail. This dual functionality of EMRE ensures that all transport-competent uniporters are tightly regulated, responding appropriately to a dynamic intracellular Ca(2+) landscape.
dc.format.extent 1 file
dc.language English
dc.language.iso eng
dc.publisher eLife Sciences Publications Ltd.
dc.relation.isversionof https://dx.doi.org/10.7554/eLife.15545
dc.rights Creative Commons Attribution 4.0 International License
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject EMRE
dc.subject MCU
dc.subject biochemistry
dc.subject calcium transport
dc.subject human
dc.subject ion channel
dc.subject mitochondria
dc.subject Calcium
dc.subject Calcium Channels
dc.subject HEK293 Cells
dc.subject Humans
dc.subject Calcium Channels
dc.subject SMDT1 protein, human
dc.subject mitochondrial calcium uniporter
dc.subject Calcium
dc.title Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex.
dc.type Article
dc.contributor.department Department of Biochemistry
dc.relation.journal eLife
dc.identifier.pmid 27099988

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