Autophagy restricts symbiosis-associated cell death and regulates colonization by Serendipita indica in Arabidopsis.

Endophytic colonization of Arabidopsis (Arabidopsis thaliana) by the beneficial root endophyte Serendipita indica is characterized by an initial biotrophic phase, followed by a confined host cell death phase that facilitates fungal accommodation. However, the host molecular pathways that restrict S. indica proliferation and regulate symbiosis-associated cell death remain largely unknown. Our study demonstrates that autophagy, a key cellular degradation pathway that maintains homeostasis, is locally activated during colonization and is required to limit fungal proliferation and immunometabolic stress. Autophagy-deficient mutants exhibit elevated basal root cell death, increased colonization, and hypersensitivity to the fungal-derived purine metabolite 2'-deoxyadenosine (dAdo), an immunometabolic signal that modulates host cell viability and reprograms immune and metabolic responses via ENT3 (equilibrative nucleoside transporter 3)-mediated uptake. In ent3 and atg5 ent3 mutants, suppression of dAdo import reduces S. indica-induced cell death, confirming the central role of ENT3-mediated uptake. Despite increased colonization and stress sensitivity, autophagy-deficient plants retain S. indica-mediated root growth promotion, indicating that mutualistic benefits can occur independently of immunometabolic stress resilience. Based on these findings, we propose that autophagy-mediated pro-survival responses are essential for maintaining symbiotic homeostasis by integrating immunometabolic signals and preserving host cell viability.