Difference between revisions of "Baughman 2011 Nature"
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{{Publication | {{Publication | ||
|title= | |title=Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341-5 | ||
|info=http://www.ncbi.nlm.nih.gov/pubmed/ | |info=[http://www.ncbi.nlm.nih.gov/pubmed/21685886 PMID: 21685886 ] | ||
|authors=Perocchi F | |authors=Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK | ||
|year= | |year=2011 | ||
|journal=Nature | |journal=Nature | ||
|abstract= | |abstract=Mitochondria from diverse organisms are capable of transporting large amounts of Ca<sup>2+</sup> via a ruthenium-red-sensitive, membrane-potential-dependent mechanism called the uniporter. Although the uniporter's biophysical properties have been studied extensively, its molecular composition remains elusive. We recently used comparative proteomics to identify MICU1 (also known as CBARA1), an EF-hand-containing protein that serves as a putative regulator of the uniporter. Here, we use whole-genome phylogenetic profiling, genome-wide RNA co-expression analysis and organelle-wide protein coexpression analysis to predict proteins functionally related to MICU1. All three methods converge on a novel predicted transmembrane protein, CCDC109A, that we now call 'mitochondrial calcium uniporter' (MCU). MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU in cultured cells or in vivo in mouse liver severely abrogates mitochondrial Ca<sup>2+</sup> uptake, whereas mitochondrial respiration and membrane potential remain fully intact. MCU has two predicted transmembrane helices, which are separated by a highly conserved linker facing the intermembrane space. Acidic residues in this linker are required for its full activity. However, an S259A point mutation retains function but confers resistance to Ru360, the most potent inhibitor of the uniporter. Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca<sup>2+</sup> uniporter. | ||
|keywords= | |keywords=Mitochondria, calcium, genomics | ||
|mipnetlab=DE Munich Perocchi F | |mipnetlab=DE Munich Perocchi F | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |area=nDNA;cell genetics, Genetic knockout;overexpression | ||
|organism=Human, Mouse, Fungi | |||
|organism=Human, Mouse, | |tissues=Endothelial;epithelial;mesothelial cell | ||
|tissues=Endothelial; | |preparations=Intact cells, Permeabilized cells, Permeabilized tissue, Isolated mitochondria | ||
|preparations=Intact | |enzymes=Inner mt-membrane transporter, TCA cycle and matrix dehydrogenases | ||
|topics=Ion;substrate transport, mt-Membrane potential | |||
|couplingstates=LEAK, OXPHOS | |couplingstates=LEAK, OXPHOS | ||
}} | }} | ||
Latest revision as of 11:08, 27 March 2018
| Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341-5 |
Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK (2011) Nature
Abstract: Mitochondria from diverse organisms are capable of transporting large amounts of Ca2+ via a ruthenium-red-sensitive, membrane-potential-dependent mechanism called the uniporter. Although the uniporter's biophysical properties have been studied extensively, its molecular composition remains elusive. We recently used comparative proteomics to identify MICU1 (also known as CBARA1), an EF-hand-containing protein that serves as a putative regulator of the uniporter. Here, we use whole-genome phylogenetic profiling, genome-wide RNA co-expression analysis and organelle-wide protein coexpression analysis to predict proteins functionally related to MICU1. All three methods converge on a novel predicted transmembrane protein, CCDC109A, that we now call 'mitochondrial calcium uniporter' (MCU). MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU in cultured cells or in vivo in mouse liver severely abrogates mitochondrial Ca2+ uptake, whereas mitochondrial respiration and membrane potential remain fully intact. MCU has two predicted transmembrane helices, which are separated by a highly conserved linker facing the intermembrane space. Acidic residues in this linker are required for its full activity. However, an S259A point mutation retains function but confers resistance to Ru360, the most potent inhibitor of the uniporter. Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca2+ uniporter. • Keywords: Mitochondria, calcium, genomics
• O2k-Network Lab: DE Munich Perocchi F
Labels: MiParea: nDNA;cell genetics, Genetic knockout;overexpression
Organism: Human, Mouse, Fungi
Tissue;cell: Endothelial;epithelial;mesothelial cell
Preparation: Intact cells, Permeabilized cells, Permeabilized tissue, Isolated mitochondria
Enzyme: Inner mt-membrane transporter, TCA cycle and matrix dehydrogenases
Regulation: Ion;substrate transport, mt-Membrane potential
Coupling state: LEAK, OXPHOS
