| Literature DB >> 29097544 |
Yusuke Hirabayashi1,2,3,4, Seok-Kyu Kwon1,2,3, Hunki Paek1,2,3, Wolfgang M Pernice5, Maëla A Paul1,2,3, Jinoh Lee1,2,3, Parsa Erfani1,2,3, Ashleigh Raczkowski6, Donald S Petrey7,8, Liza A Pon5,9, Franck Polleux10,2,3.
Abstract
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 (Ca2+) uptake by mitochondria after synaptically induced Ca2+-release from ER and thereby regulated cytoplasmic Ca2+ 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 Ca2+ dynamics in mammalian neurons.Entities:
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Year: 2017 PMID： 29097544 PMCID： PMC5818999 DOI： 10.1126/science.aan6009
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728