Role of Late Endosomal Autophagy-Dependent Secretion in Regulating ER and Mitochondrial Stress and Stress Communication

ABSTRACT: Late endosomal secretion is an unconventional mechanism that relies on VAMP7 and is upregulated in autophagy-null cells. Transcriptomic analysis of VAMP7 knockout (KO) cells revealed significant changes in the expression of genes related to the mitochondria and endoplasmic reticulum (ER) stress. We observed major morphological and functional mitochondrial defects in VAMP7KO cells both in vitro and in vivo in mouse models. Specifically, VAMP7KO cells exhibited impaired transport of mitochondrial-derived vesicles to late endosomes and reduced mitochondrial component secretion. Similarly, VAMP7 was involved in membrane trafficking from the ER to late endosomes and secretion of ER components. Pharmacological induction of stress in the ER or mitochondria led to an increased release of their respective components, in a manner dependent on both VAMP7 and autophagy. In an in vivo glioblastoma model, grafting VAMP7 KO cells into rat brains resulted in larger, more necrotic tumors with higher macrophage infiltration, whereas autophagy-null cells induced smaller and less necrotic tumors. In conclusion, late endosomal secretion plays a crucial role in maintaining ER and mitochondrial quality control and regulates tumor growth and necrosis, thus late endosomal autophagy-dependent secretion is a quality control and a stress communication mechanism.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Fibroblast

SUBMITTER: Chiara guerrera  

LAB HEAD: Thierry Galli

PROVIDER: PXD057152 | Pride | 2026-01-26

REPOSITORIES: Pride