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AI662270-GRP94 axis couples the unfolded protein response to mitochondrial dynamics during acute myocardial infarction

GSE304427 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2025/08/13 Platform GPL24247
Summary
Endoplasmic reticulum stress (ERS) response, triggered by myocardial ischemia, contributes to cardiac injury through unresolved mechanisms. Our study reveals that the chaperone GRP94 attenuates mitochondrial fragmentation and ischemic damage by inhibiting OPA1 hydrolysis to S-OPA1 post-acute myocardial infarction (AMI). Mechanistically, hypoxia induces a transcriptional switch where transcription factor YY1 dissociates from lncRNA Oip5os1 and binds lncRNA AI662270, promoting GRP94 transcription. Cardiac-specific GRP94 overexpression reduced infarct size and improved cardiac function. Conversely, GRP94 or AI662270 knockdown exacerbated injury. Furthermore, GRP94-Anxa2 interaction (identified by Co-IP/MS) activates AKT signaling to stabilize long-form OPA1 (L-OPA1), preserving mitochondrial integrity. Targeting the AI662270/GRP94/OPA1 axis thus offers a novel therapeutic strategy for acute ischemic cardiomyopathy by modulating ER-mitochondria crosstalk.
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Also filed as BioProject PRJNA1301289 and SRA study SRP606432. Searching any of these in the dataset finder brings you back here.

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