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Vol. 12, Issue 10, 3016-3030, October 2001
#
Mitochondria play a pivotal role in apoptosis in multicellular
organisms by releasing apoptogenic factors such as cytochrome c that activate the caspases effector pathway, and
apoptosis-inducing factor (AIF) that is involved in a
caspase-independent cell death pathway. Here we report that cell death
in the single-celled organism Dictyostelium discoideum
involves early disruption of mitochondrial transmembrane potential
(Department of Genetics, Development, and Molecular
Pathology, INSERM/CNRS Institut Cochin de Génétique
Moléculaire, 75014 Paris, France; *EMI U-9922
(INSERM-Université Paris VII), CHU Bichat-Claude Bernard, 75018 Paris, France; Laboratoire de Physiocochimie
Biomoléculaire et Cellulaire, CNRS ESA 7033, Université
Pierre et Marie Curie, F-75252 Paris, France; §INRA/LGPTA,
59651 Villeneuve d'Ascq Cedex, France; Laboratoire de
Photobiologie, Museum National d'Histoire Naturelle, F-75231 Paris
Cedex 05, France; and ¶Unité de Régulation
Enzymatique des Activités Cellulaires, Institut Pasteur, 75724 Paris, France
m) that precedes the induction of several apoptosis-like
features, including exposure of the phosphatidyl residues at the
external surface of the plasma membrane, an intense vacuolization, a
fragmentation of DNA into large fragments, an autophagy, and the
release of apoptotic corpses that are engulfed by neighboring cells. We
have cloned a Dictyostelium homolog of mammalian AIF
that is localized into mitochondria and is translocated from the
mitochondria to the cytoplasm and the nucleus after the onset of cell
death. Cytoplasmic extracts from dying Dictyostelium cells trigger the breakdown of isolated mammalian and
Dictyostelium nuclei in a cell-free system, and this
process is inhibited by a polyclonal antibody specific for
Dictyostelium discoideum apoptosis-inducing factor
(DdAIF), suggesting that DdAIF is involved in DNA degradation during
Dictyostelium cell death. Our findings indicate that the cell death pathway in Dictyostelium involves
mitochondria and an AIF homolog, suggesting the evolutionary
conservation of at least part of the cell death pathway in unicellular
and multicellular organisms.
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