Role of Mitochondria in Apoptosis

Apoptosis is an evolutionary‐conserved physiological mechanism to remove cells from an organism. Cellular apoptosis is mediated via an intracellular signalling programme that involves a variety of signalling molecules and cellular organelles including caspases, sphingomyelinases, Bcl‐2‐like proteins and proteins to cleave the DNA and mitochondria. Mitochondria contain several pro‐apoptotic molecules that activate cytosolic proteins to execute apoptosis, block anti‐apoptotic proteins in the cytosol and directly cleave nuclear DNA. Mitochondria trap these pro‐apoptotic proteins and physically separate pro‐apoptotic proteins from their cytoplasmic targets. Apoptosis is then initiated by the release of mitochondrial pro‐apoptotic proteins into the cytosol. This process seems to be regulated by Bcl‐2‐like proteins and several ion channels, in particular the permeability transition pore (PTP) that is activated by almost all pro‐apoptotic stimuli.

[1]  G. Kroemer,et al.  The mitochondrion in apoptosis: how Pandora's box opens , 2001, Nature Reviews Molecular Cell Biology.

[2]  David Wallach,et al.  Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death , 1996, Cell.

[3]  G. Kroemer,et al.  Mitochondrial control of nuclear apoptosis , 1996, The Journal of experimental medicine.

[4]  Xiaodong Wang,et al.  Smac, a Mitochondrial Protein that Promotes Cytochrome c–Dependent Caspase Activation by Eliminating IAP Inhibition , 2000, Cell.

[5]  Xiaodong Wang,et al.  Bid, a Bcl2 Interacting Protein, Mediates Cytochrome c Release from Mitochondria in Response to Activation of Cell Surface Death Receptors , 1998, Cell.

[6]  D. Green,et al.  The central executioners of apoptosis: caspases or mitochondria? , 1998, Trends in cell biology.

[7]  J C Reed,et al.  Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. , 1998, Science.

[8]  Andreas Villunger,et al.  Bmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis , 2001, Science.

[9]  T. Yanagida,et al.  Electrophysiological Study of a Novel Large Pore Formed by Bax and the Voltage-dependent Anion Channel That Is Permeable to Cytochrome c * , 2000, The Journal of Biological Chemistry.

[10]  A. Strasser,et al.  The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. , 1999, Molecular cell.

[11]  Ximena Opitz-Araya,et al.  Requirement for Caspase-2 in Stress-Induced Apoptosis Before Mitochondrial Permeabilization , 2002, Science.

[12]  R. Kolesnick,et al.  CD95 Signaling via Ceramide-rich Membrane Rafts* , 2001, The Journal of Biological Chemistry.

[13]  B. Calabretta,et al.  Transforming Growth Factor 1 Induces Apoptosis through Cleavage of BAD in a Smad3-Dependent Mechanism in FaO Hepatoma Cells , 2002 .

[14]  S. Cory,et al.  Life-or-death decisions by the Bcl-2 protein family. , 2001, Trends in biochemical sciences.

[15]  M. V. Heiden,et al.  Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Matthias Mann,et al.  FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling Complex , 1996, Cell.

[17]  Robert L Moritz,et al.  Identification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP Proteins , 2000, Cell.

[18]  E. Ikonen,et al.  Functional rafts in cell membranes , 1997, Nature.

[19]  Tak W. Mak,et al.  Two Distinct Pathways Leading to Nuclear Apoptosis , 2000, The Journal of experimental medicine.

[20]  H. Nakayama,et al.  A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. , 2001, Molecular cell.

[21]  Xiaodong Wang,et al.  Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c , 1996, Cell.

[22]  S. Korsmeyer,et al.  Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c , 2000, Cell Death and Differentiation.

[23]  L. Peso,et al.  Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. , 1997, Science.

[24]  M. Prevost,et al.  Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process , 1999, The Journal of experimental medicine.

[25]  Elizabeth Yang,et al.  Serine Phosphorylation of Death Agonist BAD in Response to Survival Factor Results in Binding to 14-3-3 Not BCL-XL , 1996, Cell.

[26]  A. Rebollo,et al.  Segregation of Bad from Lipid Rafts Is Implicated in the Induction of Apoptosis1 , 2002, The Journal of Immunology.

[27]  Jean-Claude Martinou,et al.  Bid-induced Conformational Change of Bax Is Responsible for Mitochondrial Cytochrome c Release during Apoptosis , 1999, The Journal of cell biology.

[28]  Masashi Narita,et al.  Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC , 1999, Nature.

[29]  Y. Tsujimoto,et al.  Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Xu Luo,et al.  Endonuclease G is an apoptotic DNase when released from mitochondria , 2001, Nature.

[31]  M. V. Vander Heiden,et al.  Bcl-x l Promotes the Open Configuration of the Voltage-dependent Anion Channel and Metabolite Passage through the Outer Mitochondrial Membrane* , 2001, The Journal of Biological Chemistry.

[32]  G. Gao,et al.  N‐terminal cleavage of Bax by calpain generates a potent proapoptotic 18‐kDa fragment that promotes Bcl‐2‐independent cytochrome C release and apoptotic cell death , 2000, Journal of cellular biochemistry.

[33]  M. V. Heiden,et al.  Bcl-xL Regulates the Membrane Potential and Volume Homeostasis of Mitochondria , 1997, Cell.

[34]  K. Murphy,et al.  Bcl-2 Inhibits a Fas-induced Conformational Change in the Bax N Terminus and Bax Mitochondrial Translocation* , 2000, The Journal of Biological Chemistry.

[35]  R. Kolesnick,et al.  Ceramide Channels Increase the Permeability of the Mitochondrial Outer Membrane to Small Proteins* , 2002, The Journal of Biological Chemistry.

[36]  Xiaodong Wang,et al.  Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3 , 1997, Cell.

[37]  A. Strasser,et al.  Bcl-2, Bcl-xL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death , 1997, Oncogene.

[38]  Ruedi Aebersold,et al.  Molecular characterization of mitochondrial apoptosis-inducing factor , 1999, Nature.

[39]  R. J. Clem,et al.  An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif , 1993, Journal of virology.

[40]  T. Chittenden,et al.  Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. , 1998, Proceedings of the National Academy of Sciences of the United States of America.