Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants

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Cross-species interactome analysis uncovers a conserved

selective autophagy mechanism for protein quality control in plants

Víctor Sánchez de Medina Hernández1,2*, Marintia Mayola Nava García1,2*, Marion Clavel1,3, Ranjith K. Papareddy1, Veselin I. Andreev1, Varsha Mathur1, Azadeh Mohseni1,4, Marta García-León1, Peng Gao1, Juan Carlos de la Concepción1, Lorenzo Picchianti1, Nenad Grujic1, Roksolana Kobylinska1, Alibek Abdrakhmanov1,2, Héloïse Duvergé1, Gaurav Anand5, Nils Leibrock1,4, Anita Bianchi1, Margot Raffeiner6, Timothy Scott Crawford7, Luca Argirò1, Mateusz Matuszkiewicz1,8, Cheuk-Ling Wun1, Jakob Valdbjørn Kanne9, Anton Meinhart10, Elisabeth Roitinger1, Isabel Bäurle7, Byung Ho Kang11, Morten Petersen9, Suayib Üstün6, Yogesh Kulathu5, Tim Clausen10, Silvia Ramundo1, Yasin Dagdas1

1 Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna BioCenter (VBC), Vienna, Austria.

2 Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, A-1030, Vienna, Austria.

3 Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.

4 Department of Applied Genetics and Cell Biology, Institute of Molecular Plant Biology, BOKU University, Vienna, Austria.

5 MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.

6 Faculty of Biology & Biotechnology, Ruhr-University of Bochum, 44780 Bochum, Germany.

7 Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany.

8 Department of Plant Genetics, Breeding and Biotechnology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, Poland.

9 Functional Genomic Section, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

10 Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.

11 School of Life Sciences, Centre for Cell & Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.

*These authors contributed equally to this work

Correspondence: Yasin Dagdas, [e-mail]

Abstract

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 proteotoxic 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.