Mechanism of Cell Death Caused by Complex I Defects in a Rat Dopaminergic Cell Line

AbstractInflammation and cell death are closely linked arms of the host immune response to infection, which when carefully balanced ensure host survival. One example of this balance is the tightly regulated transition from TNFR1-associated pro-inflammatory complex I to pro-death complex II. By contrast, here we show that a TRIF-dependent complex containing FADD, RIPK1 and caspase-8 (that we have termed the TRIFosome) mediates cell death in response to Yersinia pseudotuberculosis and LPS. Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus positioning ZBP1 as an effector of cell death in the context of bacterial blockade of pro-inflammatory signaling. Additionally, our findings offer an alternative to the TNFR1-dependent model of complex II assembly, by demonstrating pro-death complex formation reliant on TRIF signaling.

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Evaluation of the cellular protection by novel spiropyrazole compounds in dopaminergic cell death

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2020.113140 ◽

2021 ◽

pp. 113140

Author(s):

Jamila Zaiter ◽

Achraf Hibot ◽

Abderrafia Hafid ◽

Mostafa Khouili ◽

Claudia M.B. Neves ◽

...

Keyword(s):

Cell Death ◽

Dopaminergic Cell ◽

Cellular Protection

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

Biological Chemistry ◽

10.1515/hsz-2020-0254 ◽

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.

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The Human Leukemic HL-60 Cell Line: An in Vitro Model for Cell Death Endpoint Identification

Alternatives to Laboratory Animals ◽

10.1177/026119299602400419 ◽

1996 ◽

Vol 24 (4) ◽

pp. 581-587

Author(s):

Cristiana Zanetti ◽

Arrnalaura Stammati ◽

Orazio Sapora ◽

Flavia Zucco

Keyword(s):

Cell Death ◽

Cell Line ◽

In Vitro Model ◽

Leukemia Cell ◽

Promyelocytic Leukemia ◽

Leukemia Cell Line ◽

Cell Type ◽

Vitro Model ◽

Promyelocytic Leukemia Cell Line

The aim of this study was to investigate the endpoints related to cell death, either necrosis or apoptosis, induced by four chemicals in the promyelocytic leukemia cell line, HL-60. Cell morphology, DNA fragmentation, cytofluorimetric analysis and oxygen consumption were used to classify the type of cell death observed. In our analysis, we found that not all the selected parameters reproduced the differences observed in the cell death caused by the four chemicals tested. As cell death is a very complex phenomenon, several factors should be taken into account (cell type, exposure time and chemical concentration), if chemicals are to be classified according to differences in the mechanisms more directly involved in cell death.

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