Mitochondrial regulation of apoptotic cell death

被引:328
作者
Orrenius, S [1 ]
机构
[1] Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
关键词
apoptosis; cardiopipin; caspase; cytochrome c; mitochondria; toxicant;
D O I
10.1016/j.toxlet.2003.12.017
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Although it has long been known that impairment of mitochondrial function may lead to ATP depletion and necrotic cell death, recent work has revealed that these organelles also play an important role in the regulation of apoptotic cell death by mechanisms which have been conserved through evolution. Thus, it seems that a number of toxicants target the mitochondria and promote their release of cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and other parts of the apoptotic process. Cytochrome c release is governed by the Bcl-2 family of proteins, whereas subsequent caspase activation is modulated by other proteins, including inhibitor of apoptosis proteins (IAPs) and heat shock proteins. Recent findings indicate that cytochrome c extrusion occurs by a two-step process, which is initiated by a disruption of the association of the hemoprotein with cardiolipin, the phospholipid that anchors it to the outer surface of the inner mitochondrial membrane. Release of the solubilized pool of cytochrome c into the cytosol may then occur by permeabilization of the outer mitochondrial membrane mediated by pro-apoptotic Bcl-2 family proteins, notably Bax and Bak, or by Ca2+-triggered mitochondrial permeability transition. Taken together, these findings have placed the mitochondria in the focus of apoptosis research and further underlined the important function of these organelles in cell life and death. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:19 / 23
页数:5
相关论文
共 15 条
[1]   The mitochondrial permeability transition pore and its role in cell death [J].
Crompton, M .
BIOCHEMICAL JOURNAL, 1999, 341 :233-249
[2]   Cytochrome c release occurs via Ca2+-dependent and Ca2+-independent mechanisms that are regulated by Bax [J].
Gogvadze, V ;
Robertson, JD ;
Zhivotovsky, B ;
Orrenius, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (22) :19066-19071
[3]   Mitochondria and apoptosis [J].
Green, DR ;
Reed, JC .
SCIENCE, 1998, 281 (5381) :1309-1312
[4]   Role of Fas-Fas ligand interactions in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity:: Increased resistance of thymocytes from Fas-deficient (Ipr) and Fas ligand-defective (gld) mice to TCDD-induced toxicity [J].
Kamath, AB ;
Camacho, I ;
Nagarkatti, PS ;
Nagarkatti, M .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1999, 160 (02) :141-155
[5]   Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade [J].
Li, P ;
Nijhawan, D ;
Budihardjo, I ;
Srinivasula, SM ;
Ahmad, M ;
Alnemri, ES ;
Wang, XD .
CELL, 1997, 91 (04) :479-489
[6]   Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors [J].
Luo, X ;
Budihardjo, I ;
Zou, H ;
Slaughter, C ;
Wang, XD .
CELL, 1998, 94 (04) :481-490
[7]   DITHIOCARBAMATES INDUCE APOPTOSIS IN THYMOCYTES BY RAISING THE INTRACELLULAR LEVEL OF REDOX-ACTIVE COPPER [J].
NOBEL, CSI ;
KIMLAND, M ;
LIND, B ;
ORRENIUS, S ;
SLATER, AFG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (44) :26202-26208
[8]  
Ostrander DB, 2001, J BIOL CHEM, V276, P38061
[9]   Cytochrome c release from mitochondria proceeds by a two-step process [J].
Ott, M ;
Robertson, JD ;
Gogvadze, V ;
Zhivotovsky, B ;
Orrenius, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (03) :1259-1263
[10]   Reactive oxygen species generated from the mitochondrial electron transport chain induce cytochrome c dissociation from beef-heart submitochondrial particles via cardiolipin peroxidation.: Possible role in the apoptosis [J].
Petrosillo, G ;
Ruggiero, FM ;
Pistolese, M ;
Paradies, G .
FEBS LETTERS, 2001, 509 (03) :435-438