Abstract
Science. 2024 Aug 8:eadp7114. doi: 10.1126/science.adp7114. Online ahead of print.
ABSTRACT
Endoplasmic Reticulum (ER) stress induces repression of protein synthesis throughout the cell. Attempts to understand how localized stress leads to widespread repression have been limited by difficulties in resolving translation rates at the subcellular level. Here, using live-cell imaging of reporter mRNA translation, we unexpectedly found that during ER stress active translation at mitochondria was significantly protected. The mitochondrial protein, ATAD3A, interacted with PERK and mediated this effect on localized translation by competing for binding with PERK's target, eIF2. PERK-ATAD3A interactions increased during ER stress, forming mitochondria-ER contact sites. Furthermore, ATAD3A binding attenuated local PERK signaling and rescued the expression of some mitochondrial proteins. Thus, PERK-ATAD3A interactions can control translational repression at a subcellular level, mitigating the impact of ER stress on the cell.
PMID:39116259 | DOI:10.1126/science.adp7114
UK DRI Authors
