EMRE is an essential component of the mitochondrial calcium uniporter complex.
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.
Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Yasemin
Y
Sancak
Andrew L
AL
Markhard
Toshimori
T
Kitami
Erika
E
Kovács-Bogdán
Kimberli J
KJ
Kamer
Namrata D
ND
Udeshi
Steven A
SA
Carr
Dipayan
D
Chaudhuri
David E
DE
Clapham
Andrew A
AA
Li
Sarah E
SE
Calvo
Olga
O
Goldberger
Vamsi K
VK
Mootha
D000595:Amino Acid Sequence; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D020832:EF Hand Motifs; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D040901:Proteomics
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C116241:MICU1 protein, human; C582650:MICU2 protein, human; D033681:Mitochondrial Membrane Transport Proteins; C585180:SMDT1 protein, human; C034703:mitochondrial calcium uniporter