RRC ID 6673
Author Arnoult D, Tatischeff I, Estaquier J, Girard M, Sureau F, Tissier JP, Grodet A, Dellinger M, Traincard F, Kahn A, Ameisen JC, Petit PX.
Title On the evolutionary conservation of the cell death pathway: mitochondrial release of an apoptosis-inducing factor during Dictyostelium discoideum cell death.
Journal Mol Biol Cell
Abstract 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 (DeltaPsim) 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.
Volume 12(10)
Pages 3016-30
Published 2001-10-1
DOI 10.1091/mbc.12.10.3016
PMID 11598188
PMC PMC60152
MeSH Amino Acid Sequence Animals Apoptosis / physiology* Apoptosis Inducing Factor Cell Nucleus / metabolism Cell-Free System Cytosol / metabolism DNA Fragmentation / physiology Dictyostelium / physiology* Dictyostelium / ultrastructure Evolution, Molecular* Flavoproteins / chemistry Flavoproteins / genetics* Flavoproteins / metabolism* Humans Jurkat Cells Mammals / physiology Membrane Potentials / physiology Membrane Proteins / chemistry Membrane Proteins / genetics* Membrane Proteins / metabolism* Mitochondria / metabolism Molecular Sequence Data Phagocytosis / physiology Phosphatidylserines / metabolism Protoporphyrins / chemistry Protoporphyrins / metabolism* Sequence Homology
IF 3.791
Times Cited 117
Cellular slime molds G02564