title: Endosome-mitochondria interactions are modulated by iron release from transferrin.
abstract: Transient "kiss and run" interactions between endosomes containing iron-bound transferrin (Tf) and mitochondria have been shown to facilitate direct iron transfer in erythroid cells. In this study, we used superresolution three-dimensional (3D) direct stochastic optical reconstruction microscopy to show that Tf-containing endosomes directly interact with mitochondria in epithelial cells. We used live-cell time-lapse fluorescence microscopy, followed by 3D rendering, object tracking, and a distance transformation algorithm, to track Tf-endosomes and characterize the dynamics of their interactions with mitochondria. Quenching of iron sensor RDA-labeled mitochondria confirmed functional iron transfer by an interacting Tf-endosome. The motility of Tf-endosomes is significantly reduced upon interaction with mitochondria. To further assess the functional role of iron in the ability of Tf-endosomes to interact with mitochondria, we blocked endosomal iron release by using a Tf K206E/K534A mutant. Blocking intraendosomal iron release led to significantly increased motility of Tf-endosomes and increased duration of endosome-mitochondria interactions. Thus, intraendosomal iron regulates the kinetics of the interactions between Tf-containing endosomes and mitochondria in epithelial cells.
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208.
authors.forename: Anupam
authors.identifier: 0000-0003-4982-4177
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208.
authors.forename: Sagarika
authors.initials: S
authors.lastname: Nag
authors.affiliation: Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405.
authors.forename: Anne B
authors.identifier: 0000-0003-3097-4589
authors.initials: AB
authors.lastname: Mason
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208 barrosm@mail.amc.edu.
authors.forename: Margarida M
authors.initials: MM
authors.lastname: Barroso
mesh_terms: D000818:Animals; D004285:Dogs; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007501:Iron / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D059008:Time-Lapse Imaging; D014168:Transferrin / Q000378:metabolism*
chemical_list: D014168:Transferrin; D007501:Iron