PDZD8

PDZD8, or PDZ domain-containing protein 8, is a eukaryotic protein encoded by the PDZD8 gene in humans. It localizes primarily to the endoplasmic reticulum (ER) and is implicated in the formation and maintenance of inter-organelle membrane contact sites, especially ER–mitochondria contacts.

Protein architecture: PDZD8 contains an N-terminal PDZ domain, followed by coiled-coil regions, and a C-terminal SMP (synaptotagmin-like mitochondrial lipid-binding protein) domain. The SMP domain is associated with lipid transfer at membrane contact sites, a feature shared with components of the yeast ERMES complex, suggesting a lipid-exchange role at ER-linked organelles.

Function and interactions: In mammalian cells, PDZD8 is proposed to act as a tether that supports ER–mitochondria contacts, facilitating lipid transfer and possibly signaling between these organelles. It may also participate in other ER–organelle contact sites, including ER–endosome contacts, contributing to organelle positioning and trafficking. Experimental disruption of PDZD8 has been shown to affect ER–mitochondria associations and mitochondrial morphology in some cells, highlighting its role in interorganelle communication.

Research status and relevance: PDZD8 has been studied mainly in cultured mammalian cells and neural models. While no disease has been definitively linked to PDZD8, abnormalities in ER–mitochondria contact sites are implicated in neurodegenerative conditions, making PDZD8 a subject of interest for understanding cellular lipid transfer and organelle communication.