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Science DOI:10.1126/science.1242993

EMRE is an essential component of the mitochondrial calcium uniporter complex.

Publication TypeJournal Article
Year of Publication2013
AuthorsSancak, Y, Markhard, AL, Kitami, T, Kovács-Bogdán, E, Kamer, KJ, Udeshi, ND, Carr, SA, Chaudhuri, D, Clapham, DE, Li, AA, Calvo, SE, Goldberger, O, Mootha, VK
Date Published2013 Dec 13
KeywordsAmino Acid Sequence, Calcium Channels, Calcium-Binding Proteins, Cation Transport Proteins, Cell Membrane, EF Hand Motifs, Gene Knockdown Techniques, HEK293 Cells, Humans, Mitochondria, Mitochondrial Membrane Transport Proteins, Molecular Sequence Data, Phylogeny, Protein Structure, Tertiary, Proteomics

The mitochondrial uniporter is a highly selective calcium channel in the organelle's inner membrane. Its molecular components include the EF-hand-containing calcium-binding proteins mitochondrial calcium uptake 1 (MICU1) and MICU2 and the pore-forming subunit mitochondrial calcium uniporter (MCU). We sought to achieve a full molecular characterization of the uniporter holocomplex (uniplex). Quantitative mass spectrometry of affinity-purified uniplex recovered MICU1 and MICU2, MCU and its paralog MCUb, and essential MCU regulator (EMRE), a previously uncharacterized protein. EMRE is a 10-kilodalton, metazoan-specific protein with a single transmembrane domain. In its absence, uniporter channel activity was lost despite intact MCU expression and oligomerization. EMRE was required for the interaction of MCU with MICU1 and MICU2. Hence, EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium-conducting role of MCU.


Alternate JournalScience
PubMed ID24231807
PubMed Central IDPMC4091629
Grant ListF32HL107021 / HL / NHLBI NIH HHS / United States
R24 DK080261 / DK / NIDDK NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
F32 HL107021 / HL / NHLBI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
DK080261 / DK / NIDDK NIH HHS / United States