ER-mitochondria tethering by PDZD8 regulates Ca 2+ dynamics in mammalian neurons

Making the right contacts Contacts between the endoplasmic reticulum (ER) and mitochondria mediate key physiological processes such as Ca 2+ exchange and lipid biogenesis. wiIn yeast, ER and mitochondria are tethered by a complex of four proteins called ERMES. However, no functional orthologs of these ERMES complex proteins have been identified in metazoans. Hirabayashi et al. identified PDZD8 as a structural and functional ortholog of the yeast ERMES protein MMM1 (see the Perspective by Lombardi and Elrod). PDZD8 was found at ER-mitochondria contact sites and was required for ER-mitochondria tethering in mammalian cells. In neuronal dendrites, PDZD8 regulated synaptically evoked Ca 2+ dynamics, which underscores the importance of interorganelle membrane contacts in cell physiology. Science , this issue p. 623 ; see also p. 591