EMRE Is an Essential Component of the Mitochondrial Calcium Uniporter Complex

• Published in: Science (American Association for the Advancement of Science) Vol. 342; no. 6164; pp. 1379 - 1382
• Main Authors: Sancak, Yasemin, Markhard, Andrew L., Kitami, Toshimori, Kovács-Bogdán, 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.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 13.12.2013; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Biological taxonomies; Calcium; Calcium channels; Calcium Channels - chemistry; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Cell death; Cell lines; Cell Membrane - metabolism; Cellular immunity; Channels; EF Hand Motifs; Gene Knockdown Techniques; HEK293 Cells; HeLa cells; Humans; Immunoblotting; Literary Devices; Mass spectrometry; Mass spectroscopy; Metabolism; Mitochondria; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Membrane Transport Proteins - metabolism; Molecular biology; Molecular Sequence Data; Organelles; P branes; Phylogeny; Protein Structure, Tertiary; Proteins; Proteomics; Transport
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1242993

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-ki loda Ito n, m etazoa ç-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.