scholarly journals Redox- and Ligand Binding-Dependent Conformational Ensembles in the Human Apoptosis-Inducing Factor Regulate Its Pro-Life and Cell Death Functions

2019 ◽  
Vol 30 (18) ◽  
Author(s):  
Raquel Villanueva ◽  
Silvia Romero-Tamayo ◽  
Ruben Laplaza ◽  
Juan Martínez-Olivan ◽  
Adrián Velázquez-Campoy ◽  
...  
Keyword(s):  
Cell Death ◽  
Ligand Binding ◽  
Conformational Ensembles ◽  
Apoptosis Inducing Factor ◽  
Pro Life

scholarly journals Apoptosis inducing factor and mitochondrial NADH dehydrogenases: redox-controlled gear boxes to switch between mitochondrial biogenesis and cell death

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Johannes M. Herrmann ◽  
Jan Riemer
Keyword(s):  
Cell Death ◽  
Complex I ◽  
Electron Transfer Reaction ◽  
Apoptotic Protein ◽  
Transport Chain ◽  
Metabolic Conditions ◽  
Nadh Dehydrogenases ◽  
The One ◽  
Apoptosis Inducing Factor ◽  
Redox Switches

AbstractThe mitochondrial complex I serves as entry point for NADH into the electron transport chain. In animals, fungi and plants, additional NADH dehydrogenases carry out the same electron transfer reaction, however they do not pump protons. The apoptosis inducing factor (AIF, AIFM1 in humans) is a famous member of this group as it was the first pro-apoptotic protein identified that can induce caspase-independent cell death. Recent studies on AIFM1 and the NADH dehydrogenase Nde1 of baker’s yeast revealed two independent and experimentally separable activities of this class of enzymes: On the one hand, these proteins promote the functionality of mitochondrial respiration in different ways: They channel electrons into the respiratory chain and, at least in animals, promote the import of Mia40 (named MIA40 or CHCHD4 in humans) and the assembly of complex I. On the other hand, they can give rise to pro-apoptotic fragments that are released from the mitochondria to trigger cell death. Here we propose that AIFM1 and Nde1 serve as conserved redox switches which measure metabolic conditions on the mitochondrial surface and translate it into a binary life/death decision. This function is conserved among eukaryotic cells and apparently used to purge metabolically compromised cells from populations.

scholarly journals Apoptosis inducing factor (AIF): a phylogenetically old, caspase-independent effector of cell death

1999 ◽  
Vol 6 (6) ◽  
pp. 516-524 ◽  
Author(s):  
Hans Kristian Lorenzo ◽  
Santos A Susin ◽  
Josef Penninger ◽  
Guido Kroemer
Keyword(s):  
Cell Death ◽  
Apoptosis Inducing Factor

scholarly journals Hsp70 Overexpression Sequesters AIF and Reduces Neonatal Hypoxic/Ischemic Brain Injury

2005 ◽  
Vol 25 (7) ◽  
pp. 899-910 ◽  
Author(s):  
Yasuhiko Matsumori ◽  
Shwuhuey M Hong ◽  
Koji Aoyama ◽  
Yang Fan ◽  
Takamasa Kayama ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Wild Type ◽  
Hsp 70 ◽  
Artery Ligation ◽  
Ischemic Brain ◽  
Carotid Artery Ligation ◽  
High Level ◽  
Apoptosis Inducing Factor

Apoptosis is implicated in neonatal hypoxic/ischemic (H/I) brain injury among various forms of cell death. Here we investigate whether overexpression of heat shock protein (Hsp) 70, an antiapoptotic protein, protects the neonatal brain from H/I injury and the pathways involved in the protection. Postnatal day 7 (P7) transgenic mice overexpressing rat Hsp70 (Tg) and their wild-type littermates (Wt) underwent unilateral common carotid artery ligation followed by 30 mins exposure to 8% O2. Significant neuroprotection was observed in Tg versus Wt mice on both P12 and P21, correlating with a high level of constitutive but not inducible Hsp70 in the Tg. More prominent injury was observed in Wt and Tg mice on P21, suggesting its continuous evolution after P12. Western blot analysis showed that translocation of cytochrome c, but not the second mitochondria-derived activator of caspase (Smac)/DIABLO and apoptosis-inducing factor (AIF), from mitochondria into cytosol was significantly reduced in Tg 24 h after H/I compared with Wt mice. Coimmunoprecipitation detected more Hsp70 bound to AIF in Tg than Wt mice 24 h after H/I, inversely correlating with the amount of nuclear, but not cytosolic, AIF translocation. Our results suggest that interaction between Hsp70 and AIF might have reduced downstream events leading to cell death, including the reduction of nuclear AIF translocation in the neonatal brains of Hsp70 Tg mice after H/I.

scholarly journals BUB1 mediation of caspase-independent mitotic death determines cell fate

2007 ◽  
Vol 178 (2) ◽  
pp. 283-296 ◽  
Author(s):  
Yohei Niikura ◽  
Amruta Dixit ◽  
Ray Scott ◽  
Guy Perkins ◽  
Katsumi Kitagawa
Keyword(s):  
Cell Death ◽  
Cell Fate ◽  
Cell Lines ◽  
Chromosome Instability ◽  
Spindle Checkpoint ◽  
Mitotic Cell ◽  
Endonuclease G ◽  
Colon Tumors ◽  
Mitotic Death ◽  
Apoptosis Inducing Factor

The spindle checkpoint that monitors kinetochore–microtubule attachment has been implicated in tumorigenesis; however, the relation between the spindle checkpoint and cell death remains obscure. In BUB1-deficient (but not MAD2-deficient) cells, conditions that activate the spindle checkpoint (i.e., cold shock or treatment with nocodazole, paclitaxel, or 17-AAG) induced DNA fragmentation during early mitosis. This mitotic cell death was independent of caspase activation; therefore, we named it caspase-independent mitotic death (CIMD). CIMD depends on p73, a homologue of p53, but not on p53. CIMD also depends on apoptosis-inducing factor and endonuclease G, which are effectors of caspase-independent cell death. Treatment with nocodazole, paclitaxel, or 17-AAG induced CIMD in cell lines derived from colon tumors with chromosome instability, but not in cells from colon tumors with microsatellite instability. This result was due to low BUB1 expression in the former cell lines. When BUB1 is completely depleted, aneuploidy rather than CIMD occurs. These results suggest that cells prone to substantial chromosome missegregation might be eliminated via CIMD.

Nitric oxide-induced cell death in developing oligodendrocytes is associated with mitochondrial dysfunction and apoptosis-inducing factor translocation

2004 ◽  
Vol 20 (7) ◽  
pp. 1713-1726 ◽  
Author(s):  
Olivier Baud ◽  
Jianrong Li ◽  
Yumin Zhang ◽  
Rachael L. Neve ◽  
Joseph J. Volpe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Apoptosis Inducing Factor

scholarly journals Nuclear Translocation of Apoptosis-Inducing Factor after Focal Cerebral Ischemia

2004 ◽  
Vol 24 (4) ◽  
pp. 458-466 ◽  
Author(s):  
Nikolaus Plesnila ◽  
Changlian Zhu ◽  
Carsten Culmsee ◽  
Moritz Gröger ◽  
Michael A. Moskowitz ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Cytochrome C ◽  
Nuclear Translocation ◽  
Focal Cerebral Ischemia ◽  
Mitochondrial Protein ◽  
Neuronal Cell ◽  
Experimental Stroke ◽  
Cytochrome C Release ◽  
Apoptosis Inducing Factor

Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore, addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus 1 hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke.

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