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.

Simula, L., Corrado, M., Accordi, B., Di Rita, A., Nazio, F., Antonucci, Y., et al. (2020). JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction. CELL DEATH AND DIFFERENTIATION, 27(10), 2749-2767 [10.1038/s41418-020-0540-1].

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

Nazio, Francesca;Cecconi, Francesco;Campello, Silvia
2020-10-01

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.
ott-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Simula, L., Corrado, M., Accordi, B., Di Rita, A., Nazio, F., Antonucci, Y., et al. (2020). JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction. CELL DEATH AND DIFFERENTIATION, 27(10), 2749-2767 [10.1038/s41418-020-0540-1].
Simula, L; Corrado, M; Accordi, B; Di Rita, A; Nazio, F; Antonucci, Y; Di Daniele, A; Caicci, F; Caruana, I; Soriano, Me; Pigazzi, M; Locatelli, F; Cecconi, F; Campello, S
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/316762
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 15
social impact