Evolutionary Diversity of the Mitochondrial Calcium Uniporter

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Science (Impact Factor: 33.61). 05/2012; 336(6083):886. DOI: 10.1126/science.1214977
Source: PubMed


Calcium uptake into mitochondria occurs via a recently identified ion channel called the uniporter. Here, we characterize the phylogenomic distribution of the uniporter's membrane-spanning pore subunit (MCU) and regulatory partner (MICU1). Homologs of both components tend to co-occur in all major branches of eukaryotic life, but both have been lost along certain protozoan and fungal lineages. Several bacterial genomes also contain putative MCU homologs that may represent prokaryotic calcium channels. The analyses indicate that the uniporter may have been an early feature of mitochondria.

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    • "Matrix Ca 2+ uptake can be induced by abiotic stresses such as heat, oxidative stress, or anoxia, and follows the cytosolic Ca 2+ pattern (Subbaiah et al., 1998; Logan and Knight, 2003; Schwarzländer et al., 2012; Rikhvanov et al., 2014). Homologue genes of mammalian mitochondrial Ca 2+ uniporter (MCU) and its regulatory protein MICU1 have been found in plants (Bick et al., 2012; Stael et al., 2012; Rikhvanov et al., 2014). The MICU1 homologue in Arabidopsis (AtMICU) is a negative regulator of mitochondrial Ca 2+ uptake in root tips, providing strong evidence for the operation of a mitochondrial Ca 2+ uniporter in plants (Wagner et al., 2015). "
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    • "It was found that the extent of DCD was proportional to the time for which the mitochondria were polarized and therefor able to accumulate Ca 2+ (Castilho et al. 1998). The identification of the mitochondrial Ca 2+ uniporter (Patron et al. 2013; Bick et al. 2012), and the resultant ability to manipulate uniporter expression in primary neuronal culture, has allowed more elegant and less invasive experiments to be performed. Studies by Hardingham et al. (Qiu et al. 2013) in which expression levels of the mitochondrial Ca 2+ uniporter were manipulated in primary neuronal cultures, found that the extent of NMDA-induced cell death increased with overexpression of the uniporter, in parallel with increased matrix calcium accumulation, while knockdown had a neuroprotective effect. "
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    • "Protein sequences from 138 eukaryotic organisms corresponding to the published phylogenetic tree (Bick et al., 2012) were downloaded as follows: 132 species from the KEGG Organisms Database, release 58 (Kanehisa et al., 2006) and six species (Thecamonas trahens, Capsaspora owczarzaki, Sphaeroforma arctica, Salpingoeca rosetta, Allomyces macrogynus, and Spizellomyces punctatus) from the Origins of Multicellularity Sequencing Project at the Broad Institute (7/9/2012; Ruiz-Trillo et al., 2007). For each of the ten reference genomes, a species-centric binary phylogenetic matrix X g,i was constructed to contain 1 if reference gene g shared sequence similarity with any protein in species i (BLASTP; expect < 1 3 10 À3 ) and 0 otherwise. "
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