Macroautophagy inhibition maintains fragmented mitochondria to foster T cell receptor-dependent apoptosis

Mauro Corrado, Francesca R. Mariotti, Laura Trapani, Lucia Taraborrelli, Francesca Nazio, Valentina Cianfanelli, Maria Eugenia Soriano, Emilie Schrepfer, Francesco Cecconi, Luca Scorrano, Silvia Campello

Research output: Contribution to journalArticlepeer-review


Mitochondrial dynamics and functionality are linked to the autophagic degradative pathway under several stress conditions. However, the interplay between mitochondria and autophagy upon cell death signalling remains unclear. The T-cell receptor pathway signals the so-called activation-induced cell death (AICD) essential for immune tolerance regulation. Here, we show that this apoptotic pathway requires the inhibition of macroautophagy. Protein kinase-A activation downstream of T-cell receptor signalling inhibits macroautophagy upon AICD induction. This leads to the accumulation of damaged mitochondria, which are fragmented, display remodelled cristae and release cytochrome c, thereby driving apoptosis. Autophagy-forced reactivation that clears the Parkin-decorated mitochondria is as effective in inhibiting apoptosis as genetic interference with cristae remodelling and cytochrome c release. Thus, upon AICD induction regulation of macroautophagy, rather than selective mitophagy, ensures apoptotic progression.

Original languageEnglish
Pages (from-to)1793-1809
Number of pages17
JournalEMBO Journal
Issue number16
Publication statusPublished - Aug 15 2016


  • AICD
  • autophagy
  • mitochondrial dynamics
  • T cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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