2025/12/01 by Víctor Sánchez de Medina Hernández, Marintia M Nava-García, A.T.J. Bianchi +33 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Autophagy in Disease and Therapy #Endoplasmic Reticulum Stress and Disease #Ubiquitin and proteasome pathways
paper · doi:10.1016/j.devcel.2025.11.001
openalex created_date 2025/12/01 · openalex publication_date 2025/12/01 · openalex updated_date 2026/07/22
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 recruit specific cargo for degradation. Although significant strides have been made in understanding the molecular framework of selective autophagy, the diversity of SAR repertoires across species remains 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 coupling of ubiquitin to endoplasmic reticulum degradation- and protein rich in the amino acids E, L, K, and S-domain-containing SAR (CESAR) as a conserved SAR critical for proteostasis under heat stress. CESAR specifically facilitates the degradation of ubiquitinated protein aggregates and is indispensable for heat stress tolerance. Altogether, our study establishes a robust pipeline and a rich resource for SAR discovery. It also positions CESAR as a pivotal regulator of proteostasis, with broad implications for improving stress resilience in plants.