Publication Date:
2013-11-16
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091629/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091629/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sancak, Yasemin -- Markhard, Andrew L -- Kitami, Toshimori -- Kovacs-Bogdan, Erika -- Kamer, Kimberli J -- Udeshi, Namrata D -- Carr, Steven A -- Chaudhuri, Dipayan -- Clapham, David E -- Li, Andrew A -- Calvo, Sarah E -- Goldberger, Olga -- Mootha, Vamsi K -- DK080261/DK/NIDDK NIH HHS/ -- F32 HL107021/HL/NHLBI NIH HHS/ -- F32HL107021/HL/NHLBI NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- R24 DK080261/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1379-82. doi: 10.1126/science.1242993. Epub 2013 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24231807" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Calcium Channels/chemistry/genetics/*metabolism
;
Calcium-Binding Proteins/genetics/*metabolism
;
Cation Transport Proteins/genetics/*metabolism
;
Cell Membrane/*metabolism
;
EF Hand Motifs
;
Gene Knockdown Techniques
;
HEK293 Cells
;
Humans
;
Mitochondria/*metabolism
;
Mitochondrial Membrane Transport Proteins/genetics/*metabolism
;
Molecular Sequence Data
;
Phylogeny
;
Protein Structure, Tertiary
;
Proteomics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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