First Author | Hirabayashi Y | Year | 2017 |
Journal | Science | Volume | 358 |
Issue | 6363 | Pages | 623-630 |
PubMed ID | 29097544 | Mgi Jnum | J:248462 |
Mgi Id | MGI:6094720 | Doi | 10.1126/science.aan6009 |
Citation | Hirabayashi Y, et al. (2017) ER-mitochondria tethering by PDZD8 regulates Ca(2+) dynamics in mammalian neurons. Science 358(6363):623-630 |
abstractText | Interfaces between organelles are emerging as critical platforms for many biological responses in eukaryotic cells. In yeast, the ERMES complex is an endoplasmic reticulum (ER)-mitochondria tether composed of four proteins, three of which contain a SMP (synaptotagmin-like mitochondrial-lipid binding protein) domain. No functional ortholog for any ERMES protein has been identified in metazoans. Here, we identified PDZD8 as an ER protein present at ER-mitochondria contacts. The SMP domain of PDZD8 is functionally orthologous to the SMP domain found in yeast Mmm1. PDZD8 was necessary for the formation of ER-mitochondria contacts in mammalian cells. In neurons, PDZD8 was required for calcium ion (Ca(2+)) uptake by mitochondria after synaptically induced Ca(2+)-release from ER and thereby regulated cytoplasmic Ca(2+) dynamics. Thus, PDZD8 represents a critical ER-mitochondria tethering protein in metazoans. We suggest that ER-mitochondria coupling is involved in the regulation of dendritic Ca(2+) dynamics in mammalian neurons. |