(54) ON THE EVOLUTIONARY CONSERVATION OF THE CELL DEATH MACHINERY:  INVOLVEMENT OF AN APOPTOSIS INDUCING FACTOR HOMOLOG IN Dictyostelium discoideum CELL DEATH

P.X. Petit¹*, D. Arnoult², J. Estaquier², J.P. Tissier³, A. Grodet², M. Dellinger⁴, J-C. Ameisen² and A. Kahn^1
1Department of Genetics, Development and Molecular Pathology, Institut Cochin de Génétique Moléculaire, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France
²INSERM EPI 9922, Faculté de Médecine Bichat-Claude Bernard, 16 rue Henri Huchard, 75018 Paris, France
³INRA/LGPTA, 369 rue Jules Guesde, 59651 Villeneuve d'Ascq Cedex
⁴Laboratoire de Photobiologie, Museum National d'Histoire Naturelle, 43, rue Cuvier, 75231 Paris, France

Mitochondria play a pivotal role in apoptosis in multicellular organisms by releasing apoptogenic factors such as cytochrome c and Apoptosis Inducing Factor (AIF). The cell death of the unicellular organism Dictyostelium discoideum (Dd) induced by protoporphyrin IX in presence of light or actinomycin D has several apoptosis-like features. These features include the disruption of the mitochondrial transmembrane potential (Dym), exposure of the phosphatidyl residues at the external surface of the plasma membrane, intense vacuolization, and loss of DNA content, but no oligonucleosomal DNA fragmentation. 

These events are accompanied by pronounced autophagy and release of pseudo apoptotic corpses that are engulfed by neighboring cells. We have cloned a putative cell death effector that is a Dd mitochondrial flavoprotein homolog of mammalian AIF. Here we show that DdAIF is translocated from the mitochondria to the cytoplasm after the onset of cell death. Cytoplasmic extracts from dying Dd cells triggered the breakdown of isolated Dictyostelium and mammalian nuclei in a cell free extracts system, and this process was inhibited by a polyclonal antibody specific for DdAIF. We believe that DdAIF is an evolutionary cell death inducer because its overexpression causes apoptosis in mammalian 293T cells. 

Our findings indicate that the cell death machinery in Dd involves mitochondria and an AIF homologue, suggesting the evolutionary conservation of a least part of the cell death machinery in the cells of both unicellular and multicellular organisms.
 

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