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The discovery of regulated cell death (RCD) revolutionized chemotherapy. With caspase-dependent apoptosis initially being thought to be the only form of RCD, many drug development strategies aimed to synthesize compounds that turn on this kind of cell death. While yielding a variety of drugs, this approach is limited, given the acquired resistance of cancers to these drugs and the lack of specificity of the drugs for targeting cancer cells alone. The discovery of non-apoptotic forms of RCD is leading to new avenues for drug design. Evidence shows that ferroptosis, a relatively recently discovered iron-based cell death pathway, has therapeutic potential for anticancer application. Recent studies point to the interrelationship between iron and other essential metals, copper and zinc, and the disturbance of their respective homeostasis as critical to the onset of ferroptosis. Other studies reveal that several coordination complexes of non-iron metals have the capacity to induce ferroptosis. This collective knowledge will be assessed to determine how chelation approaches and coordination chemistry can be engineered to program ferroptosis in chemotherapy.
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Dynamic death decisions: How mitochondrial dynamics shape cellular commitment to apoptosis and ferroptosis
The incorporation of mitochondria into early eukaryotes established organelle-based biochemistry and enabled metazoan development. Diverse mitochondrial biochemistry is essential for life and its homeostatic control via mitochondrial dynamics supports organelle quality and function. Mitochondria crosstalk with numerous regulated cell death (RCD) pathways to control the decision to die. In this review, we will focus on apoptosis and ferroptosis, two distinct forms of RCD, that utilize divergent signaling to kill a targeted cell. We will highlight how proteins and processes involved in mitochondrial dynamics maintain biochemically diverse subcellular compartments to support apoptosis and ferroptosis machinery; as well as unite disparate RCD pathways through dual control of organelle biochemistry and the decision to die.
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- Award ID(s):
- 2217138
- PAR ID:
- 10649199
- Publisher / Repository:
- Cell Press
- Date Published:
- Journal Name:
- Developmental Cell
- Volume:
- 59
- Issue:
- 19
- ISSN:
- 1534-5807
- Page Range / eLocation ID:
- 2549 to 2565
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.devcel.2024.09.004
