Lipid droplets and small extracellular vesicles: More than two independent entities

Géraldine C. Genard, Luca Tirinato*, Francesca Pagliari, Jessica Da Silva, Alessandro Giammona, Fatema Alquraish, Maria Parra Reyes, Marie Bordas, Maria Grazia Marafioti, Simone Di Franco, Jeannette Janssen, Daniel Garcia-Calderón, Rachel Hanley, Clelia Nistico, Yoshinori Fukasawa, Torsten Müller, Jeroen Krijgsveld, Matilde Todaro, Francesco Saverio Costanzo, Giorgio StassiMichelle Nessling, Karsten Richter, Kendra K. Maass, Carlo Liberale*, Joao Seco*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Despite increasing knowledge about small extracellular vesicle (sEV) composition and functions in cell–cell communication, the mechanism behind their biogenesis remains unclear. Here, we reveal for the first time that sEV biogenesis and release into the microenvironment are tightly connected with another important organelle, Lipid Droplets (LDs). The correlation was observed in several human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results demonstrated that external stimuli such as radiation, pH, hypoxia or lipid-interfering drugs, known to affect the number of LDs/cell, similarly influenced sEV secretion. Importantly, through multiple omics data, at both mRNA and protein levels, we revealed RAB5C as a potential important molecular player behind this organelle connection. Altogether, the potential to fine-tune sEV biogenesis by targeting LDs could significantly impact the amount, cargos and properties of these sEVs, opening new clinical perspectives.

Original languageEnglish (US)
Article numbere162
JournalJournal of Extracellular Biology
Volume3
Issue number9
DOIs
StatePublished - Sep 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

Keywords

  • exosomes
  • hypoxia
  • iron metabolism
  • irradiation
  • lipid droplets
  • pH
  • Rab
  • small extracellular vesicles

ASJC Scopus subject areas

  • Cell Biology

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