UDTR — Radar mondial des droits de la Nature

Dfm1 promotes Ste24-dependent translocon quality control

Identification

Clé publique

radar:r-66282090b0ffd921e447775e93e1dffb

Auteurs

James A. Avaala · Sophia L. Owutey · Connor G Bailey · Kathryn L Alexander · Karen E. Alexander · Melissa Palackel · Travis S Beckett · Katrina A Procuniar · Kyle A. Richards · Kelsey A. Woodruff · Katie M. Lehman · Kaikeyi M Paxton · Sudheeksha Bommineni · Emmanuel Akoto · Samantha M. Turk · Jacob M Miller · Hailey J Barton · Eric S. Fults · Robert J. Tomko · Eric M. Rubenstein

Année déclarée

2026

Langue déclarée

en

Type source

preprint

Première détection

2026-11-13T12:50:55.861893+00:00

Dernière observation des métadonnées

2026-11-13T12:50:55.861893+00:00

Dernière vérification HTTP

Non effectuée

Institutions déclarées par la source

Ball State University · Florida State University · Purdue University West Lafayette · University of Minnesota · University of Washington · Fred Hutch Cancer Center · St. Jude Children's Research Hospital · Columbus Regional Healthcare System

Pays d’affiliation déclarés

US

Résumé documentaire — langue originale

Abstract Proteins stalled during endoplasmic reticulum translocation clog Sec61 channels and require translocon quality control (TQC) mechanisms for clearance. Genetic screens implicated the derlin Dfm1 in TQC; however, its mechanistic role remained unclear. Using engineered and disease-relevant translocon-clogging substrates in Saccharomyces cerevisiae , we show Dfm1 functions in the Ste24-dependent branch of TQC, but not Hrd1- or Ltn1-dependent pathways. Loss of DFM1 increased accumulation and toxicity of translocon-clogging proteins. Increased dosage of wild type or catalytically inactive Hrd1 or Ste24 rescued toxicity, supporting a non-enzymatic buffering function for these factors in TQC. These findings identify Dfm1 as a key TQC factor whose critical role in clearing clogged translocons can be suppressed in multiple ways. Our results suggest enhancing TQC may protect cells from proteotoxic stress caused by disease-relevant translocon-clogging substrates, with potential implications for pancreatic β-cell dysfunction in diabetes. Significance Statement Cells rely on translocon quality control (TQC) to clear proteins that clog the Sec61 translocon, but how the derlin Dfm1 contributes to this process has remained unclear. We demonstrate that Dfm1 functions specifically in the Ste24-dependent TQC pathway and show that increased levels of the TQC factors Hrd1 or Ste24 rescues Dfm1 deficiency even without catalytic activity, revealing an unexpected non-enzymatic buffering function. This work defines Dfm1’s mechanistic role in TQC, provides new insight into how cells preserve endoplasmic reticulum function during translocation stress, and establishes a framework for investigating conserved pathways that protect against diseases associated with translocon clogging.

Identifiants

OPENALEX

https://openalex.org/W7167056214

DOI

10.64898/2026.07.01.735875

Repères documentaires

Famille documentaire

unknown

Types déclarés par les sources

preprint

Les mentions d’entités ne constituent pas une preuve de reconnaissance juridique. La juridiction étudiée est distincte du pays d’affiliation des auteurs.

Sources

OpenAlex · Document 1

• Document · https://doi.org/10.64898/2026.07.01.735875

Statut documentaire

Pertinence à examiner

Bibliothèque

Cette identité n’est pas encore intégrée à la Bibliothèque juridique.