Mitochondria and programmed cell death: back to the future

FEBS Letters

Mignotte, Bernard²  Petit, Patrice X.²  Zamzami, Naoufal¹  Susin, Santos-Antonio¹  Kroemer, Guido¹ 

[1] CNRS-UPR 420, 19 rue Guy Môquet, BP 8, F-94801 Villejuif, France;Centre de Génétique Moléculaire, CGM, CNRS UPR 2420, avenue de la Terrasse, Bâtiment 24, F-91198 Gif-sur-Yvette, France

关键词: Apoptosis;    Bcl-2;    Mitochondria;    Permeability transition pore;    Protease;    AIF;    apoptosis inducing factor;    ΔΨ m;    mitochondrial membrane potential;    ICE;    interleukin-1β converting enzyme;    PCD;    programmed cell death;    PT;    permeability transition pore;    ROS;    reactive oxygen species;    TNF;    tumor necrosis factor;   

DOI  :  10.1016/0014-5793(96)00988-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Programmed cell death, or apoptosis, has in the past few years undoubtedly become one of the most intensively investigated biological processes. However, fundamental questions concerning the molecular and biochemical mechanisms remain to be elucidated. The central question concerns the biochemical steps shared by the numerous death induction pathways elicited by different stimuli. Heterogeneous death signals precede a common effector phase during which cells pass a threshold of ‘no return’ and are engaged in a degradation phase where they acquire the typical onset of late apoptosis. Alterations in mitochondrial permeability transition linked to membrane potential disruption precede nuclear and plasma membrane changes. In vitro induction of permeability transition in isolated mitochondria provokes the release of a protein factor capable of inducing nuclear chromatin condensation and fragmentation. This permeability transition is regulated by multiple endogenous effectors, including members of the bcl-2 gene family. Inhibition of these effects prevents apoptosis.

【 授权许可】

Unknown