Endosome-mitochondria interactions are modulated by iron release from transferrin

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• Endosomes containing iron-bound transferrin (Tf) transiently interact with mitochondria.
• These interactions facilitate direct iron transfer, particularly noted in erythroid cells.

Purpose of the Study:

• To investigate the interaction dynamics between Tf-containing endosomes and mitochondria in epithelial cells.
• To elucidate the role of intraendosomal iron in regulating these interactions.

Main Methods:

• Superresolution 3D direct stochastic optical reconstruction microscopy (3D-dSTORM).
• Live-cell time-lapse fluorescence microscopy with 3D rendering and object tracking.
• Iron sensor quenching (RDA) and Tf mutant (K206E/K534A) to assess iron transfer and release.

Main Results:

• Tf-containing endosomes directly interact with mitochondria in epithelial cells.
• Mitochondrial iron transfer was confirmed via functional assays.
• Endosome-mitochondria interactions reduced Tf-endosome motility.
• Blocking intraendosomal iron release increased Tf-endosome motility and interaction duration.

Conclusions:

• Intraendosomal iron release is a key regulator of Tf-endosome and mitochondria interaction kinetics.
• This mechanism highlights a direct role for iron in cellular trafficking and organelle communication.
• Findings extend the understanding of iron homeostasis beyond erythroid cells to epithelial systems.