Uncovering the initial response: Intra-mitochondrial surveillance activates the UPRmt - PubMed
5 hours ago
- #UPRmt activation
- #mitochondrial surveillance
- #oxidative stress
- The mitochondrial unfolded protein response (UPRmt) protects against proteotoxic stress, but current models involve severe disruption and cytosolic detection.
- A chemogenetic strategy in yeast induced mild mitochondrial oxidative stress via hydrogen peroxide, activating UPRmt independently of cytosolic damage.
- Oxidative stress causes glutathionylation of cysteines in presequence proteases MPP and Oct1, impairing activity and leading to unprocessed precursor accumulation.
- These precursors form proteotoxic aggregates in the matrix, which are detected by intra-mitochondrial surveillance, triggering UPRmt signaling as a primary response.