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

ABSTRACT: 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 effect

SUBMITTER: Corrado M 

PROVIDER: S-EPMC5010050 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature