ArticleInternational journal of molecular sciences2022
The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- OPA1 as a Cancer Target: Molecular Mechanisms, Structural Insights, and Strategies for Drug Development.Antioxidants (Basel, Switzerland) · 2026Review
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- FAM172A promotes epithelial ovarian cancer progression and induces platinum resistance via the PI3K/AKT pathway.Scientific reports · 2025Article
- Unlocking the mitochondrial functional code: unraveling the pathogenesis of ovarian cancer and innovative targets to inhibit malignant behavior.Journal of translational medicine · 2025Review
- mTOR inhibition triggers mitochondrial fragmentation in cardiomyocytes through proteosome-dependent prohibitin degradation and OPA-1 cleavage.Cell communication and signaling : CCS · 2025Article
- Emerging roles of prohibitins in cancer: an update.Cancer gene therapy · 2025Review
- Optic Atrophy 1: The Conductor of Cellular Harmony and Age-Related Pathologies.Aging and disease · 2025Review
- Knowledge, Attitudes, and Practices of Patients from the Anesthesia Clinic in Jinshan District, Shanghai, Regarding Visiting the Anesthesia Clinic.Patient preference and adherence · 2025Article
- Inhibition of mitochondrial OMA1 ameliorates osteosarcoma tumorigenesis.Cell death & disease · 2024Article
- OMA1-Mediated Mitochondrial Dynamics Balance Organellar Homeostasis Upstream of Cellular Stress Responses.International journal of molecular sciences · 2024Review
- DELE1 haploinsufficiency causes resistance to mitochondrial stress-induced apoptosis in monosomy 5/del(5q) AML.Leukemia · 2024Article
- Mitochondrial stress: a key role of neuroinflammation in stroke.Journal of neuroinflammation · 2024Review
- Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.Frontiers in immunology · 2024Review
- Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy.Cancer biology & medicine · 2023Review
- The Prohibitin-Binding Compound Fluorizoline Activates the Integrated Stress Response through the eIF2α Kinase HRI.International journal of molecular sciences · 2023Article
- Review
- A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer.Journal of Zhejiang University. Science. B · 2023Article
- Ovarian Cancer: A Landscape of Mitochondria with Emphasis on Mitochondrial Dynamics.International journal of molecular sciences · 2023Review
- Death associated protein‑3 (DAP3) and DAP3 binding cell death enhancer‑1 (DELE1) in human colorectal cancer, and their impacts on clinical outcome and chemoresistance.International journal of oncology · 2023Article
- Increased Mobile Zinc Regulates Retinal Ganglion Cell Survival via Activating Mitochondrial OMA1 and Integrated Stress Response.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Interactions between the mitochondrial inner and outer membranes and between mitochondria and other organelles closely correlates with the sensitivity of ovarian cancer to cisplatin and other chemotherapeutic drugs. However, the underlying mechanism remains unclear. Recently, the mitochondrial protease OMA1, which regulates internal and external signals in mitochondria by cleaving mitochondrial proteins, was shown to be related to tumor progression. Therefore, we evaluated the effect of OMA1 on the response to chemotherapeutics in ovarian cancer cells and the mouse subcutaneous tumor model. We found that OMA1 activation increased ovarian cancer sensitivity to cisplatin in vivo and in vitro. Mechanistically, in ovarian cancer, OMA1 cleaved optic atrophy 1 (OPA1), leading to mitochondrial inner membrane cristae remodeling. Simultaneously, OMA1 induced DELE1 cleavage and its cytoplasmic interaction with EIF2AK1. We also demonstrated that EIF2AK1 cooperated with the ER stress sensor EIF2AK3 to amplify the EIF2S1/ATF4 signal, resulting in the rupture of the mitochondrial outer membrane. Knockdown of OMA1 attenuated these activities and reversed apoptosis. Additionally, we found that OMA1 protease activity was regulated by the prohibitin 2 (PHB2)/stomatin-like protein 2 (STOML2) complex. Collectively, OMA1 coordinates the mitochondrial inner and outer membranes to induce ovarian cancer cell death. Thus, activating OMA1 may be a novel treatment strategy for ovarian cancer.
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