Work

ER-driven Contact Sites in Autophagosome Biogenesis Sequence

Year: 2026

Type: article

Abstract: formation and expansion of the phagophore, yet the cellular principles governing its spatial and temporal organization remain incompletely understood. Accumulating evidence now places the endoplasmic reticulum (ER) at the center of this process, not merely as a membrane source, but as a dynamic scaffold that organizes phagophore assembly through extensive membrane contact sites with multiple organelles. ER-mediated contacts with endosomes, mitochondria, the plasma membrane, and ER-Golgi intermediates create specialized microenvironments that integrate signaling, lipid transfer, vesicle formation and trafficking, and biophysical constraints to drive phagophore nucleation and growth. These contact sites enable the coordinated mobilization of diverse membrane carriers and autophagy regulators in a stress- and context-dependent manner. In this review, we discuss how ER-driven membrane contact sites orchestrate autophagosome biogenesis, highlight emerging mechanistic and biophysical concepts, and consider their broader implications for cellular stress adaptation and disease.

Source: Contact

DOI: 10.1177/25152564261451671

Authors: Juliane Da Graça, Dobrawa Amiri Czajkowski, Etienne Morel

Institutions: Centre National de la Recherche Scientifique, Inserm, Université Paris Cité, Institut Necker Enfants Malades, École Polytechnique Fédérale de Lausanne

Language: English

Topic: Autophagy in Disease and Therapy

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $850

Funders: Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique