Lorenzo Picchianti

RNA viruses co-opt host endomembranes to form replication complexes, often triggering cellular stress and immune responses. Here, we show that Arabidopsis thaliana activates selective autophagy to respond to viruses targeting mitochondria, chloroplasts, and the endoplasmic reticulum. Rather than degrading viral components, autophagy selectively removes the immune regulator Enhanced Disease Susceptibility 1 (EDS1) to prevent cell death. This targeted mechanism is mediated by oligomeric metabolic enzymes that moonlight as selective autophagy receptors, linking organelle stress to immune homeostasis. Our findings establish selective autophagy as an essential immune rheostat that fine-tunes defense responses and safeguards cellular integrity to promote host survival during viral infections.

Selective autophagy is a fundamental protein quality control pathway that safeguards proteostasis by degrading damaged or surplus cellular components, particularly under stress. This process is orchestrated by selective autophagy receptors (SARs) that direct specific cargo for degradation. While significant strides have been made in understanding the molecular framework of selective autophagy, the diversity of SAR repertoires across species remain largely unexplored. Through a comparative interactome analysis across five model organisms, we identified a suite of conserved and lineage-specific SAR candidates. Among these, we validated CESAR as a conserved SAR critical for proteostasis under heat stress. CESAR specifically facilitates the degradation of hydrophobic, ubiquitinated protein aggregates and is indispensable for heat stress tolerance. Our study offers a rich resource for SAR discovery and positions CESAR as a pivotal regulator of proteostasis, with broad implications for improving stress resilience in plants.

: RNA viruses co-opt the host endomembrane system and organelles to build replication complexes for infection. How the host responds to these membrane perturbations is poorly understood. Here, we explore the autophagic response of Arabidopsis thaliana to three viruses that hijack different cellular compartments. Autophagy is significantly induced within systemically infected tissues, its disruption rendering plants highly sensitive to infection. Contrary to being an antiviral defense mechanism as previously suggested, quantitative analyses of the viral loads established autophagy as a tolerance pathway. Further analysis of one of these viruses, the Turnip Crinkle Virus (TCV) that hijack mitochondria, showed that despite perturbing mitochondrial integrity, TCV does not trigger a typical mitophagy response. Instead, TCV and Turnip yellow mosaic virus (TYMV) infection activates a distinct selective autophagy mechanism, where oligomeric metabolic enzymes moonlight as selective autophagy receptors and degrade key executors of defense and cell death such as EDS1. Altogether, our study reveals an autophagy-regulated metabolic rheostat that gauges cellular integrity during viral infection and degrades cell death executors to avoid catastrophic amplification of immune signaling.

Plants rely on autophagy and membrane trafficking to tolerate stress, combat infections, and maintain cellular homeostasis. However, the molecular interplay between autophagy and membrane trafficking is poorly understood. Using an AI-assisted approach, we identified Rab3GAP-like (Rab3GAPL) as an important membrane trafficking node that controls plant autophagy negatively. Rab3GAPL suppresses autophagy by binding to ATG8, the core autophagy adaptor, and deactivating Rab8a, a small GTPase essential for autophagosome formation and defense-related secretion. Rab3GAPL from Nicotiana benthamiana , but not its mutated form deficient in ATG8 binding, reduced autophagic flux in N. benthamiana and Arabidopsis. Furthermore, Rab3GAPL -knockout mutants of the liverwort Marchantia polymorpha exhibited enhanced autophagic flux under both normal and heat stress conditions, suggesting that Rab3GAPL’s negative regulatory role in autophagy is conserved in land plants. Beyond autophagy regulation, Rab3GAPL modulates focal immunity against the oomycete pathogen Phytophthora infestans by preventing defense-related secretion. Altogether, our results suggest that Rab3GAPL acts as a molecular rheostat to coordinate autophagic flux and defense-related secretion by restraining Rab8a-mediated trafficking. This unprecedented interplay between a RabGAP-Rab pair and ATG8 sheds new light on the intricate membrane transport mechanisms underlying plant autophagy and immunity.