ArticleMolecular biology of the cell2007
Loss of caspase-9 reveals its essential role for caspase-2 activation and mitochondrial membrane depolarization.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Molecular Profiling and Selective Pro-Apoptotic Activity of a Pruning-DerivedInternational journal of molecular sciences · 2026Article
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- Research progress on the adverse effects of high-altitude environment to the male reproductive system: a review study.Frontiers in endocrinology · 2025Review
- Novel 4-alkoxy Meriolin Congeners Potently Induce Apoptosis in Leukemia and Lymphoma Cells.Molecules (Basel, Switzerland) · 2024Article
- Targeting mitochondrial metabolism by the mitotoxin bromoxib in leukemia and lymphoma cells.Cell communication and signaling : CCS · 2024Article
- Novel meriolin derivatives activate the mitochondrial apoptosis pathway in the presence of antiapoptotic Bcl-2.Cell death discovery · 2024Article
- Pathogen-driven nucleotide overload triggers mitochondria-centered cell death in phagocytes.PLoS pathogens · 2023Article
- The Connection Between Selected Caspases Levels in Bronchoalveolar Lavage Fluid and Severity After Brain Injury.Frontiers in neurology · 2022Article
- Deorphanizing Caspase-3 and Caspase-9 Substrates In and Out of Apoptosis with Deep Substrate Profiling.ACS chemical biology · 2021Article
- The Role of Caspase-2 in Regulating Cell Fate.Cells · 2020Review
- Age-associated changes in human CD4Aging · 2019Article
- Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis.Cell death & disease · 2019Article
- Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7.Science advances · 2019Article
- Memantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of KCell communication and signaling : CCS · 2019Article
- N-(3-Oxo-acyl)-homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts.Cellular microbiology · 2018Article
- Conotoxin MVIIA improves cell viability and antioxidant system after spinal cord injury in rats.PloS one · 2018Article
- Modulatory effects of Terminalia arjuna against domoic acid induced toxicity in Caco-2 cell line.Cytotechnology · 2017Article
- The antihypertensive drug hydralazine activates the intrinsic pathway of apoptosis and causes DNA damage in leukemic T cells.Oncotarget · 2016Article
- The Influence of C-Ions and X-rays on Human Umbilical Vein Endothelial Cells.Frontiers in oncology · 2016Article
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Authors and funding
4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Caspase-9 plays an important role in apoptosis induced by genotoxic stress. Irradiation and anticancer drugs trigger mitochondrial outer membrane permeabilization, resulting in cytochrome c release and caspase-9 activation. Two highly contentious issues, however, remain: It is unclear whether the loss of the mitochondrial membrane potential DeltaPsi(M) contributes to cytochrome c release and whether caspases are involved. Moreover, an unresolved question is whether caspase-2 functions as an initiator in genotoxic stress-induced apoptosis. In the present study, we have identified a mutant Jurkat T-cell line that is deficient in caspase-9 and resistant to apoptosis. Anticancer drugs, however, could activate proapoptotic Bcl-2 proteins and cytochrome c release, similarly as in caspase-9-proficient cells. Interestingly, despite these alterations, the cells retained DeltaPsi(M). Furthermore, processing and enzyme activity of caspase-2 were not observed in the absence of caspase-9. Reconstitution of caspase-9 expression restored not only apoptosis but also the loss of DeltaPsi(M) and caspase-2 activity. Thus, we provide genetic evidence that caspase-9 is indispensable for drug-induced apoptosis in cancer cells. Moreover, loss of DeltaPsi(M) can be functionally separated from cytochrome c release. Caspase-9 is not only required for DeltaPsi(M) loss but also for caspase-2 activation, suggesting that these two events are downstream of the apoptosome.
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