Correspondence to B. Mignotte, Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, F-91198 Gif-sur-Yvette cedex, France
Mitochondria and apoptosis
Article first published online: 25 DEC 2001
European Journal of Biochemistry
Volume 252, Issue 1, pages 1–15, February (II) 1998
How to Cite
Mignotte, B. and Vayssiere, J.-L. (1998), Mitochondria and apoptosis. European Journal of Biochemistry, 252: 1–15. doi: 10.1046/j.1432-1327.1998.2520001.x
Abbreviations.Δ@KYm, mitochondrial membrane potential; PCD, programmed cell death; caspases, cysteine aspartases; PT, permeability transition; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α; NGF, nerve growth factor; NF-κB, nuclear factor-κB; AIF, apoptosis inducing factor; Apaf-1, apoptosis protease-activating factor 1; ANT, adenine nucleotides translocase; GSH, glutathione; IL-3, interleukin-3.
Note. This Review will be reprinted in EJB Reviews 1998 which will be available in April 1999.
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- (Received 10 December 1997)
- Cited By
- programmed cell death;
Programmed cell death serves as a major mechanism for the precise regulation of cell numbers and as a defense mechanism to remove unwanted and potentially dangerous cells. Despite the striking heterogeneity of cell death induction pathways, the execution of the death program is often associated with characteristic morphological and biochemical changes, and this form of programmed cell death has been termed apoptosis.
Genetic studies in Caenorhabditis elegans had led to the identification of cell death genes (ced). The genes ced-3 and ced-4 are essential for cell death; ced-9 antagonizes the activities of ced-3 and ced-4, and thereby protects cells that should survive from any accidental activation of the death program. Caspases (cysteine aspartases) are the mammalian homologues of CED-3. CED-9 protein is homologous to a family of many members termed the Bcl-2 family (Bcl-2s) in reference to the first discovered mammalian cell death regulator. In both worm and mammalian cells, the antiapoptotic members of the Bcl-2 family act upstream of the execution caspases somehow preventing their proteolytic processing into active killers.
Two main mechanisms of action have been proposed to connect Bcl-2s to caspases. In the first one, antiapoptotic Bcl-2s would maintain cell survival by dragging caspases to intracellular membranes (probably the mitochondrial membrane) and by preventing their activation. The recently described mammalian protein Apaf-1 (apoptosis protease-activating factor 1) could be the mammalian equivalent of CED-4 and could be the physical link between Bcl-2s and caspases. In the second one, Bcl-2 would act by regulating the release from mitochondria of some caspases activators : cytochrome c and/or AIF (apoptosis-inducing factor). This crucial position of mitochondria in programmed cell death control is reinforced by the observation that mitochondria contribute to apoptosis signaling via the production of reactive oxygen species. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of programmed cell death. In this review, we examine the data concerning the mitochondrial features of apoptosis. Furthermore, we discuss the possibility that the mechanism originally involved in the maintenance of the symbiosis between the bacterial ancestor of the mitochondria and the host cell precursor of eukaryotes, provided the basis for the actual mechanism controlling cell survival.