| First Author | Corrado M | Year | 2016 |
| Journal | EMBO J | Volume | 35 |
| Issue | 16 | Pages | 1793-809 |
| PubMed ID | 27390127 | Mgi Jnum | J:235061 |
| Mgi Id | MGI:5792741 | Doi | 10.15252/embj.201593727 |
| Citation | Corrado M, et al. (2016) Macroautophagy inhibition maintains fragmented mitochondria to foster T cell receptor-dependent apoptosis. EMBO J 35(16):1793-809 |
| abstractText | 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. |
