ArticleInternational journal of molecular sciences2023
The Prohibitin-Binding Compound Fluorizoline Activates the Integrated Stress Response through the eIF2α Kinase HRI.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Targeting prohibitins activates the ISR through DELE1-HRI by impairing protein import into the mitochondrial matrix.Cell death and differentiation · 2026Article
- Small GTP-binding protein GDP dissociation stimulator influences cisplatin-induced acute kidney injury via PERK-dependent ER stress.Communications biology · 2024Article
- Metabolic signature and response to glutamine deprivation are independent of p53 status in B cell malignancies.iScience · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Fluorizoline is a synthetic molecule that induces apoptosis, by selectively targeting prohibitins (PHBs), through induction of the BH3-only protein NOXA. This induction is transcriptionally regulated by the integrated stress response (ISR)-related transcription factors ATF3 and ATF4. Here, we evaluate the role of the four eIF2α kinases, to decipher which is responsible for the mechanism of ISR activation triggered by fluorizoline in HeLa and HAP1 cells. First, we demonstrated the involvement of the eIF2α kinases using ISR inhibitor (ISRIB) and by simultaneous downregulation of all four eIF2α kinases, as both approaches were able to increase cell resistance to fluorizoline-induced apoptosis. Furthermore, we confirmed that fluorizoline treatment results in endoplasmic reticulum (ER) stress, as evidenced by PERK activation. Despite PERK activation, this kinase was not directly involved in the ISR activation by fluorizoline. In this regard, we found that the eIF2α kinases are capable of compensating for each other's loss of function. Importantly, we demonstrated that the mitochondrial-stress-related eIF2α kinase HRI mediates ISR activation after fluorizoline treatment.
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Registered trials
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