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JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction.

ABSTRACT: The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control.

SUBMITTER: Simula L

PROVIDER: S-EPMC7492225 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction.

Simula Luca L Corrado Mauro M Accordi Benedetta B Di Rita Anthea A Nazio Francesca F Antonucci Ylenia Y Di Daniele Arianna A Caicci Federico F Caruana Ignazio I Soriano Maria Eugenia ME Pigazzi Martina M Locatelli Franco F Cecconi Francesco F Campello Silvia S

Cell death and differentiation 20200428 10

The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterat ...[more]

PMID: 32346136

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JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction.

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JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction.

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