Selective autophagy fine-tunes Stat92E activity by degrading Su(var)2-10/PIAS during glial injury signalling in Drosophila

Glial immunity plays a pivotal role in the maintenance of nervous system homeostasis and responses to stress conditions, including neural injuries. In Drosophila melanogaster , the transcription factor Stat92E is activated in glial cells following central nervous system injury, independently of the canonical JAK/STAT pathway, to shape glial reactivity towards degenerated axons. However, the upstream regulatory mechanisms governing Stat92E activation remain elusive. Here, we reveal a selective autophagy-mediated regulation of Stat92E in glia by the degradation of the Stat92E repressor Su(var)2-10, a member of the PIAS SUMO ligase family. Atg8a, a core autophagy factor co-localizes and interacts with Su(var)2-10. Su(var)2-10 elimination is required for efficient Stat92E-dependent transcription after injury. Furthermore, we demonstrate that autophagy is essential for the upregulation of immune pathways, exemplified by virus-induced RNA 1 ( vir-1 ), in glial cells following axon injury. We propose that Stat92E function is gated both by activating phosphorylation and autophagic Su(var)2-10 breakdown to licence glial reactivity. These findings underscore the critical role of autophagy in glial immunity and its potential impact on neural injury responses.