Mitochondria as multifaceted regulators of cell death

By F. Bock, S. Tait. Nature reviews. Molecular cell biology, 2019

2,115 citations recorded by the source corpus.

Through their many and varied metabolic functions, mitochondria power life. Paradoxically, mitochondria also have a central role in apoptotic cell death. Upon induction of mitochondrial apoptosis, mitochondrial outer membrane permeabilization (MOMP) usually commits a cell to die. Apoptotic signalling downstream of MOMP involves cytochrome c release from mitochondria and subsequent caspase activation. As such, targeting MOMP in order to manipulate cell death holds tremendous therapeutic potential across different diseases, including neurodegenerative diseases, autoimmune disorders and cancer. In this Review, we discuss new insights into how mitochondria regulate apoptotic cell death. Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions. As we highlight, together with new findings demonstrating cell survival following MOMP, this pro-inflammatory role suggests that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions. Finally, we discuss the importance and roles of mitochondria in other forms of regulated cell death, including necroptosis, ferroptosis and pyroptosis. Collectively, these new findings offer exciting, unexplored opportunities to target mitochondrial regulation of cell death for clinical benefit. Mitochondria are key executioners of apoptosis. However, it has recently become clear that beyond driving apoptosis, mitochondria also contribute to pro-inflammatory signalling and other types of regulated cell death. These functions are relevant to disease and could be targeted in the treatment of, for example, degenerative disorders, infection and cancer.

View Paper: https://www.semanticscholar.org/paper/72682effef41eb8ab86575b229f24b73ed978153

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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

1. L. Galluzzi
2. S. Marchi
3. Yao Zong
4. E. Guilbaud
5. Dahua Fan
6. T. Yamazaki
7. Hao Li
8. S. Tait

Citations in the corpus

• Nanomedicine in cancer therapy (2023, background): “391 Various lethal signal transduction cascades converge on mitochondria and make them a pivotal modulator of the intrinsic apoptotic pathway.”
• Regulated cell death (RCD) in cancer: key pathways and targeted therapies (2022, background): “Cyt-C/Apaf-1 are the essential classical pathway in the initiation of apoptosis in mitochondria.(115,116) In the process of apoptosis, the permeability of mitochondrial intima was increased, and the mitochondrial membrane potential was reduced, which promoted the release of proapoptotic factors such”
• Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “AMPK relies on PGC-1 α to signi fi cantly in fl uence GLUT4 and mitochondrial gene expression in skeletal muscle, and it activates PGC-1 α through direct phosphorylation at threonine-177 and serine-538.”
• Flavonoids as Anticancer Agents (2020, background): “There is emerging evidence that cancer is a metabolic disease determined by various degrees of mitochondrial dysfunctions and metabolic alterations [38,39,41].”
• Mitochondrial DNA in inflammation and immunity (2020, unknown): “During programmed cell death, the pro-apoptotic proteins BAX and BAK permeabilise the mitochondrial outer membrane to allow the passage of pro-apoptotic molecules to move from the inner membrane space into the cytosol, where they can initiate a caspase cascade, resulting in a rapid cell death [59].”
• Mitochondrial control of inflammation (2022, background): “placement of BaX or BaK1 from inhibitory interactions with Bcl-2, BclXl or mcl1 (ref.(45)) (see the figure, panel a).”