Where and how do mammalian cells shape autophagosomes?

Apr 9, 2026The Journal of biological chemistry

Where and how mammal cells form autophagosomes

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Autophagosomes primarily form from recycling endosomes rather than the endoplasmic reticulum.

Autophagy is essential for degrading and recycling cellular components, influencing development and survival under stress.
The process is implicated in various diseases, including neurodegeneration and cancer.
WIPI2, a key protein in autophagy, requires both phosphatidylinositol 3-phosphate and RAB11A for its recruitment to initiate autophagosome formation.
Recent observations show that the precursors of autophagosomes have a finger-like structure instead of a spherical shape.
The formation of autophagosomes involves their closure after engulfing contents, which is critical for their release from recycling endosome membranes.
A major Alzheimer’s disease gene may disrupt the final step of autophagosome formation.

AI simplified

Autophagy is a fundamental cellular process responsible for degrading and recycling cytoplasmic components and regulates homeostasis, development, and survival under stress. Autophagy plays critical roles in diseases including neurodegeneration, cancers, and various infectious and inflammatory conditions. While the molecular machinery of autophagy has been well studied, increasing evidence highlights a complex interplay between autophagy and endocytosis. Traditionally, mammalian autophagosomes were believed to originate from compartments closely associated with the endoplasmic reticulum (ER), or the ER itself. However, more recent research has demonstrated that the recycling endosome serves as the main platform for autophagosome formation. The recruitment of WIPI2, an essential autophagy protein, to autophagosome initiation sites depends on its coincident detection of phosphatidylinositol 3-phosphate (PI(3)P) and RAB11A, a recycling endosome marker. This enables conjugation of LC3 (microtubule-associated protein light-chain 3) family members to the recycling endosome membranes to become nascent autophagosomes. These findings underscore the critical role of RAB11- compartment in autophagosome biogenesis. Contrary to the conventional model that has inferred that autophagosomes derive from spherical precursors with single apertures, structured illumination microscopy reveals these precursors are finger-like structures - much like a hand grasping an object. We will describe the experimental path that led to an understanding of how autophagosomes form from outgrowths of the recycling endosomes, then close after engulfing their contents. This step is a prerequisite for the final step of autophagosome formation, the release of autophagosomes from the recycling endosome membranes, a process that is perturbed by a major Alzheimer's disease gene.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Where and how do mammalian cells shape autophagosomes?

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief