On the evolutionary conservation of the cell death pathway: mitochondrial release of an apoptosis-inducing factor during Dictyostelium discoideum cell death.
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.
Arnoult
D
D
EMI U-9922 (INSERM-Université Paris VII), CHU Bichat-Claude Bernard, 75018 Paris, France.
Tatischeff
I
I
Estaquier
J
J
Girard
M
M
Sureau
F
F
Tissier
J P
JP
Grodet
A
A
Dellinger
M
M
Traincard
F
F
Kahn
A
A
Ameisen
J C
JC
Petit
P X
PX
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D002467:Cell Nucleus / Q000378:metabolism; D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation / Q000502:physiology; D004023:Dictyostelium / Q000502:physiology* / Q000648:ultrastructure; D019143:Evolution, Molecular; D005420:Flavoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008322:Mammals / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000502:physiology; D010718:Phosphatidylserines / Q000378:metabolism; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism*; D017385:Sequence Homology
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; D011524:Protoporphyrins