Abstract
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.