Posttranscriptional gene silencing (PTGS) mediated by siRNAs is an evolutionarily conserved antiviral defense mechanism in higher plants and invertebrates. In this mechanism, viral-derived siRNAs are incorporated into the RNA-induced silencing complex (RISC) to guide degradation of the corresponding viral RNAs. In Arabidopsis, a key component of RISC is ARGONAUTE1 (AGO1), which not only binds to siRNAs but also carries the RNA slicer activity. At present little is known on post-translational mechanisms regulating AGO1 turnover. We recently reported that the viral suppressor of RNA silencing protein P0 triggers AGO1 degradation by the autophagy pathway. Moreover, this pathway also degrades AGO1 in a non-viral context, especially when the production of miRNAs is impaired. These results demonstrate that a selective process such as ubiquitylation can lead to the degradation of a key regulatory protein such as AGO1 by a degradation process generally believed to be unspecific. This novel degradation pathway may become of particular importance in situations where miRNA/siRNA populations quickly change and RISC re-programming is expected.