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Mitochondrial Regulation of Cell Death

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Mitochondrial Biology and Experimental Therapeutics

Abstract

Mitochondria are multifaceted organelles exerting vital as well as lethal functions within eukaryotic cells. When fueled with substrates and oxygen, mitochondria govern metabolic pathways, regulate calcium fluxes and are deeply involved in redox homeostasis. In stress conditions, notably when calcium and redox balances are altered, mitochondria sense cellular damages and ultimately, can orchestrate some phylogenetically-conserved forms of cell death such as intrinsic apoptosis, parthanatos as well as mitochondrial permeability transition-mediated necrosis. In contrast, they do not influence other cell death modalities such as necroptosis and ferroptosis. The execution of these mitochondria-dependent lethal processes involves the expression of mitochondria or nucleus-encoded proteins such as BCL-2 family members, VDAC, ANT, cytochrome c, Smac/Diablo, as well as Omi/HtrA2. In addition, mitochondria can also influence the cell fate through fusion/fission of the mitochondrial network and mitophagy to eliminate damaged mitochondria. Here, we will review and discuss basic knowledge on the role of mitochondria in the complex regulation of cell death.

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Acknowledgments

C.B. is funded by ANR (ANR-13-ISV1-0001-01) and the Investment for the Future program ANR-11-IDEX-0003-01 within the LABEX ANR-10-LABX-0033. D.L. is funded by scholarship from Chine Scientific Council (CSC). This work was supported by funds from Agence Nationale de la Recherche (ANR-10-IBHU-0001, ANR-10-LABX33 and ANR-11-IDEX-003-01), Electricité de France, Fondation Gustave Roussy, Institut National du Cancer (INCA 9414), Cancéropôle Ile de France, NATIXIS, SIDACTION and the French National Agency for Research on AIDS and viral Hepatitis (ANRSH) (to J-L.P.).

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Authors and Affiliations

  1. INSERM UMR-S 1180-LabEx LERMIT, Université Paris-Sud, Université Paris-Saclay, Châtenay Malabry, France

    Dawei Liu & Catherine Brenner

  2. Cell Death and Aging Team, Gustave Roussy, Villejuif, France

    Jean-Luc Perfettini

  3. Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, Villejuif, France

    Jean-Luc Perfettini

  4. Université Paris Sud - Paris Saclay, Villejuif, France

    Jean-Luc Perfettini

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  1. Dawei Liu
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  2. Jean-Luc Perfettini
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  3. Catherine Brenner
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  1. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Paulo J. Oliveira

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Liu, D., Perfettini, JL., Brenner, C. (2018). Mitochondrial Regulation of Cell Death. In: Oliveira, P. (eds) Mitochondrial Biology and Experimental Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-73344-9_6

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