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

Víctor Sánchez de Medina Hernández; Marintia M. Nava-García; Anita Bianchi; Marion Clavel; Ranjith K. Papareddy; Lina Benchalel; Veselin I. Andreev; Varsha Mathur; Azadeh Mohseni; Marta García-León; Peng Gao; Juan Carlos de la Concepción; Lorenzo Picchianti; Nenad Grujic; Roksolana Kobylinska; Alibek Abdrakhmanov; Héloïse Duvergé; Gaurav Anand; Nils Leibrock; Juncai Ma; Margot Raffeiner; Timothy Scott Crawford; Luca Argirò; Mateusz Matuszkiewicz; Cheuk Ling Wun; Jakob Valdbjørn Kanne; Anton Meinhart; Elisabeth Roitinger; Isabel Bäurle; Byung Ho Kang; Morten Petersen; Suayib Üstün; Yogesh Kulathu; Tim Clausen; Silvia Ramundo; Yasin Dagdas

doi:10.1016/j.devcel.2025.11.001

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

Víctor Sánchez de Medina Hernández (Lead / Corresponding author)
, Marintia M. Nava-García
, Anita Bianchi
, Marion Clavel
, Ranjith K. Papareddy
, Lina Benchalel
, Veselin I. Andreev
, Varsha Mathur
, Azadeh Mohseni
, Marta García-León
, Peng Gao
, Juan Carlos de la Concepción
, Lorenzo Picchianti
, Nenad Grujic
, Roksolana Kobylinska
, Alibek Abdrakhmanov
, Héloïse Duvergé
, Gaurav Anand
, Nils Leibrock
, Juncai Ma

Margot Raffeiner, Timothy Scott Crawford, Luca Argirò, Mateusz Matuszkiewicz, Cheuk Ling Wun, Jakob Valdbjørn Kanne, Anton Meinhart, Elisabeth Roitinger, Isabel Bäurle, Byung Ho Kang, Morten Petersen, Suayib Üstün, Yogesh Kulathu, Tim Clausen, Silvia Ramundo, Yasin Dagdas

MRC PPU

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English
Journal	Developmental Cell
Early online date	1 Dec 2025
DOIs	https://doi.org/10.1016/j.devcel.2025.11.001
Publication status	E-pub ahead of print - 1 Dec 2025

Keywords

aggrephagy
ATG8
autophagic flux
heat stress
protein aggregate
proteostasis
proteotoxic stress
receptor evolution
selective autophagy
selective autophagy receptor

ASJC Scopus subject areas

Molecular Biology
General Biochemistry,Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2025.11.001Licence: CC BY

Final Published VersionFinal published version, 43.2 MBLicence: CC BY

Cite this

Sánchez de Medina Hernández, V., Nava-García, M. M., Bianchi, A., Clavel, M., Papareddy, R. K., Benchalel, L., Andreev, V. I., Mathur, V., Mohseni, A., García-León, M., Gao, P., de la Concepción, J. C., Picchianti, L., Grujic, N., Kobylinska, R., Abdrakhmanov, A., Duvergé, H., Anand, G., Leibrock, N., ... Dagdas, Y. (2025). Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants. Developmental Cell. Advance online publication. https://doi.org/10.1016/j.devcel.2025.11.001

@article{ba55549132ab435fafa330951138d480,

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

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 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.",

keywords = "aggrephagy, ATG8, autophagic flux, heat stress, protein aggregate, proteostasis, proteotoxic stress, receptor evolution, selective autophagy, selective autophagy receptor",

author = "\{S{\'a}nchez de Medina Hern{\'a}ndez\}, V{\'i}ctor and Nava-Garc{\'i}a, \{Marintia M.\} and Anita Bianchi and Marion Clavel and Papareddy, \{Ranjith K.\} and Lina Benchalel and Andreev, \{Veselin I.\} and Varsha Mathur and Azadeh Mohseni and Marta Garc{\'i}a-Le{\'o}n and Peng Gao and \{de la Concepci{\'o}n\}, \{Juan Carlos\} and Lorenzo Picchianti and Nenad Grujic and Roksolana Kobylinska and Alibek Abdrakhmanov and H{\'e}lo{\"i}se Duverg{\'e} and Gaurav Anand and Nils Leibrock and Juncai Ma and Margot Raffeiner and Crawford, \{Timothy Scott\} and Luca Argir{\`o} and Mateusz Matuszkiewicz and Wun, \{Cheuk Ling\} and Kanne, \{Jakob Valdbj{\o}rn\} and Anton Meinhart and Elisabeth Roitinger and Isabel B{\"a}urle and Kang, \{Byung Ho\} and Morten Petersen and Suayib {\"U}st{\"u}n and Yogesh Kulathu and Tim Clausen and Silvia Ramundo and Yasin Dagdas",

note = "Copyright: {\textcopyright} 2025 The Authors.",

year = "2025",

month = dec,

day = "1",

doi = "10.1016/j.devcel.2025.11.001",

language = "English",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

}

Sánchez de Medina Hernández, V, Nava-García, MM, Bianchi, A, Clavel, M, Papareddy, RK, Benchalel, L, Andreev, VI, Mathur, V, Mohseni, A, García-León, M, Gao, P, de la Concepción, JC, Picchianti, L, Grujic, N, Kobylinska, R, Abdrakhmanov, A, Duvergé, H, Anand, G, Leibrock, N, Ma, J, Raffeiner, M, Crawford, TS, Argirò, L, Matuszkiewicz, M, Wun, CL, Kanne, JV, Meinhart, A, Roitinger, E, Bäurle, I, Kang, BH, Petersen, M, Üstün, S, Kulathu, Y, Clausen, T, Ramundo, S & Dagdas, Y 2025, 'Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants', Developmental Cell. https://doi.org/10.1016/j.devcel.2025.11.001

TY - JOUR

T1 - Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants

AU - Sánchez de Medina Hernández, Víctor

AU - Nava-García, Marintia M.

AU - Bianchi, Anita

AU - Clavel, Marion

AU - Papareddy, Ranjith K.

AU - Benchalel, Lina

AU - Andreev, Veselin I.

AU - Mathur, Varsha

AU - Mohseni, Azadeh

AU - García-León, Marta

AU - Gao, Peng

AU - de la Concepción, Juan Carlos

AU - Picchianti, Lorenzo

AU - Grujic, Nenad

AU - Kobylinska, Roksolana

AU - Abdrakhmanov, Alibek

AU - Duvergé, Héloïse

AU - Anand, Gaurav

AU - Leibrock, Nils

AU - Ma, Juncai

AU - Raffeiner, Margot

AU - Crawford, Timothy Scott

AU - Argirò, Luca

AU - Matuszkiewicz, Mateusz

AU - Wun, Cheuk Ling

AU - Kanne, Jakob Valdbjørn

AU - Meinhart, Anton

AU - Roitinger, Elisabeth

AU - Bäurle, Isabel

AU - Kang, Byung Ho

AU - Petersen, Morten

AU - Üstün, Suayib

AU - Kulathu, Yogesh

AU - Clausen, Tim

AU - Ramundo, Silvia

AU - Dagdas, Yasin

PY - 2025/12/1

Y1 - 2025/12/1

N2 - 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.

AB - 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.

KW - aggrephagy

KW - ATG8

KW - autophagic flux

KW - heat stress

KW - protein aggregate

KW - proteostasis

KW - proteotoxic stress

KW - receptor evolution

KW - selective autophagy

KW - selective autophagy receptor

UR - https://www.scopus.com/pages/publications/105025137987

U2 - 10.1016/j.devcel.2025.11.001

DO - 10.1016/j.devcel.2025.11.001

M3 - Article

C2 - 41330383

AN - SCOPUS:105025137987

SN - 1534-5807

JO - Developmental Cell

JF - Developmental Cell

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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