
ミトコンドリア未折りたたみタンパク質応答の活性化は、ストレス顆粒の動的な形成を調節し、ミトコンドリアの恒常性を維持する。


coremsg

To rapidly adapt to harmful changes to their environment, cells activate the integrated stress response (ISR). This results in an adaptive transcriptional and translational rewiring, and the formation of biomolecular condensates named stress granules (SGs), to resolve stress. In addition to this first line of defence, the mitochondrial unfolded protein response (UPRmt) activates a specific transcriptional programme to maintain mitochondrial homeostasis. We present evidence that SGs and UPRmt pathways are intertwined and communicate with each other. UPRmt induction results in eIF2α phosphorylation and the initial and transient formation of SGs, which subsequently disassemble. We show that the induction of GADD34 during late UPRmt protects cells from prolonged stress by impairing further assembly of SGs. Furthermore, mitochondrial respiration is enhanced during UPRmt activation when SGs are absent, suggesting that UPRmt-induced SGs have an adverse effect on mitochondrial homeostasis. These findings point to a novel crosstalk between SGs and the UPRmt that may contribute to restoring mitochondrial functions under stressful conditions.

Summary statement We describe a novel crosstalk between the mitochondrial unfolded protein response and the integrated stress response involving stress granules that protects cells from further stress.

### Competing Interest Statement

The authors have declared no competing interest.

Activation of the mitochondrial unfolded protein response regulates the dynamic formation of stress granules

ミトコンドリア未折りたたみタンパク質応答の活性化は-ストレス顆粒の動的な形成を調節する


ミトコンドリア未折りたたみタンパク質応答の活性化は、ストレス顆粒の動的な形成を調節する
