Molecular characterization of mitochondrial apoptosis-inducing factor

  title={Molecular characterization of mitochondrial apoptosis-inducing factor},
  author={Santos A. Susin and Hans K Lorenzo and Naoufal Zamzami and Isabel Marzo and Bryan E. Snow and Greg M Brothers and Joan Mangion and Etienne Daniel Jacotot and Paola Costantini and Markus Loeffler and Nathanael Larochette and David R. Goodlett and Ruedi Aebersold and D. Siderovski and Josef M. Penninger and Guido Kroemer},
Mitochondria play a key part in the regulation of apoptosis (cell death). Their intermembrane space contains several proteins that are liberated through the outer membrane in order to participate in the degradation phase of apoptosis. Here we report the identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei. AIF is a flavoprotein of relative molecular mass 57,000 which shares homology with the bacterial oxidoreductases; it is… 
Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death?
The crystal structures of both human and mouse AIF have been determined, and the fine mechanisms accounting for its oxidoreductase activity and its electrostatic interaction with double-stranded DNA have been elucidated, indicating the central role of mitochondria in the control of physiological and pathological cell demise.
Analysis of pro-apoptotic protein trafficking to and from mitochondria.
The procedures that can be used to study the subcellular location of different pro-apoptotic proteins to be used in basic cell biology and toxicology studies are described.
Toxic proteins released from mitochondria in cell death
The precise mode of action and importance of cytochrome c in apoptosis in mammalian cells has become clear through biochemical, structural and genetic studies, and more recently identified factors, for example HtrA2/OMI and Smac/DIABLO, are still being studied intensively in order to delineate their functions in apoptoses.
Mitochondrio‐nuclear translocation of AIF in apoptosis and necrosis
  • E. Daugas, S. Susin, G. Kroemer
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2000
Data are compatible with the hypothesis that AIF is a caspase‐independent mitochondrial death effector responsible for partial chromatinolysis, and in conditions of ATP depletion, AIF translocation correlates with the appearance of large‐scale DNA fragmentation.
Molecular characterization of a complex of apoptosis-inducing factor 1 with cytochrome c oxidase of the mitochondrial respiratory chain
The discovery of the previously overlooked COX-AIFM12 complex and clues provided by the structural model hint at potential roles of AIFM1 in oxidative phosphorylation biogenesis and in programmed cell death.
The Intrinsic Pathway of Apoptosis
In this chapter, the various components of the intrinsic pathway are reviewed, alterations in this pathway in various cancers are described, and evidence that some of these same antiapoptotic alterations might contribute to anticancer drug resistance under certain circumstances is discussed.
Heat Shock Protein 70 Neutralizes Apoptosis-Inducing Factor
Programmed cell death (apoptosis) is the physiological process responsible for the demise of superfluous, aged, damaged, mutated, and ectopic cells. Its normal function is essential both for
Molecular Mechanisms of Apoptosis Induced by Cytotoxic Chemicals
The current understanding of the role of apoptosis in environmental toxicant-induced cell death, using dioxin, metals (cadmium and methylmercury), organotin compounds, dithiocarbamates, and benzene as specific examples is described.
Mitochondrial involvement in cell death: release of pro-apoptotic proteins
The main goal of this project was to investigate the involvement of mitochondria in cell death and reveal a novel role for the HCN2 channel in cellDeath signaling and uncover a new potential therapeutic drug target.


Bcl-2 inhibits the mitochondrial release of an apoptogenic protease
It is shown that mitochondria contain a pre-formed approximately 50-kD protein which is released upon delta psi m disruption and which, in a cell-free in vitro system, causes isolated nuclei to undergo apoptotic changes such as chromatin condensation and internucleosomal DNA fragmentation, and the effect of Bcl-2 on the formation, release, and action of AIF.
Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process
The data suggest that caspase-2 and -9 zymogens are essentially localized in mitochondria and that the disruption of the outer mitochondrial membrane occurring early during apoptosis may be critical for their subcellular redistribution and activation.
Mitochondrial control of nuclear apoptosis
Direct evidence is presented indicating that mitochondrial PT constitutes a critical early event of the apoptotic process, and a specific ligand of the mitochondrial adenine nucleotide translocator, bongkreik acid, inhibits PT and reduces apoptosis induction by mitochondria in a cell-free system.
The Central Executioner of Apoptosis: Multiple Connections between Protease Activation and Mitochondria in Fas/APO-1/CD95- and Ceramide-induced Apoptosis
A protease activation pathway with the mitochondrial phase of apoptosis regulation is connected, providing a plausible explanation of why Bcl-2 fails to interfere with Fas-triggered apoptosis in most cell types, yet prevents ceramide- and prooxidant-induced apoptosis.cmk.
A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells and seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity.
Cytochrome c activation of CPP32‐like proteolysis plays a critical role in a Xenopus cell‐free apoptosis system
In a cell‐free system based on Xenopus egg extracts, Bcl‐2 blocks apoptotic activity by preventing cytochrome c release from mitochondria, which induces apoptosis by activating CPP32‐like caspases, via unknown cytosolic factors.
The Caspase-3 Precursor Has a Cytosolic and Mitochondrial Distribution: Implications for Apoptotic Signaling
It is proposed that the mitochondrial subpopulation of caspase-3 precursor molecules is coupled to a distinct subset of apoptotic signaling pathways that are Bcl-2 sensitive and that are transduced through multiple mitochondrion-specific protein interactions.
Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis.
The proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.
Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD‐specific caspase activation and independently of mitochondrial transmembrane depolarization
It is reported that cytochrome c release from mitochondria is an early event in the apoptotic process induced by UVB irradiation or staurosporine treatment in CEM or HeLa cells, preceding or at the time of DEVD‐specific caspase activation and substrate cleavage.