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Endosome – mitochondria interactions are modulated by iron release from transferrin

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ABSTRACT

Using superresolution and quantitative fluorescence microscopy, Das et al. have revealed that iron-transferrin–containing endosomes directly interact with mitochondria, facilitating iron transfer in epithelial cells. Their findings further enrich the repertoire of organelle–organelle direct interactions to accomplish a functional significance.

No MeSH data available.


Lock-hTf–endosomes interacting with mitochondria have increased speeds. (A) Percent frequency distribution of overall instantaneous speeds (during kiss and run phases combined) of interacting hTf-endosomes versus lock-hTf–endosomes indicates that lock-hTf–endosomes have higher motility. (B) The mean instantaneous speed of lock-hTf–endosomes was significantly higher than that of hTf-endosomes. (C) Percent frequency distribution of endosomal track speeds (total length of track divided by time taken to form the track) of interacting hTf-endosomes versus lock-hTf–endosomes also indicate higher speeds for the lock-hTf–endosomes. (D) The mean track speed of the lock-hTf–endosomes was significantly higher than that of the hTf-endosomes. (E and F) The percent frequency distribution of track lengths for hTf- and lock-hTf–endosomes was similar (E), and the difference between their mean track lengths (F) was not statistically significant. (G and H) The percent frequency distribution of track displacement lengths (the shortest linear distance between the starting and ending point of a track) for hTf- and lock-hTf–endosomes was also similar (G), and the difference between their mean values (H) was not statistically significant. Error bars: 95% confidence interval; **, P < 0.001, Student’s t test. (I) Interacting hTf-endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. (J) Interacting lock-hTf–endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. Bars, 10 µm.
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fig6: Lock-hTf–endosomes interacting with mitochondria have increased speeds. (A) Percent frequency distribution of overall instantaneous speeds (during kiss and run phases combined) of interacting hTf-endosomes versus lock-hTf–endosomes indicates that lock-hTf–endosomes have higher motility. (B) The mean instantaneous speed of lock-hTf–endosomes was significantly higher than that of hTf-endosomes. (C) Percent frequency distribution of endosomal track speeds (total length of track divided by time taken to form the track) of interacting hTf-endosomes versus lock-hTf–endosomes also indicate higher speeds for the lock-hTf–endosomes. (D) The mean track speed of the lock-hTf–endosomes was significantly higher than that of the hTf-endosomes. (E and F) The percent frequency distribution of track lengths for hTf- and lock-hTf–endosomes was similar (E), and the difference between their mean track lengths (F) was not statistically significant. (G and H) The percent frequency distribution of track displacement lengths (the shortest linear distance between the starting and ending point of a track) for hTf- and lock-hTf–endosomes was also similar (G), and the difference between their mean values (H) was not statistically significant. Error bars: 95% confidence interval; **, P < 0.001, Student’s t test. (I) Interacting hTf-endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. (J) Interacting lock-hTf–endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. Bars, 10 µm.

Mentions: Blocking iron release from Tf prevents iron-mediated conformational changes in the Tf–TfR complex (Eckenroth et al., 2011), thus allowing us to test whether an altered cargo conformation affects the motility of Tf-endosomes that interact with mitochondria. Surprisingly, lock-hTf–endosomes interacting with mitochondria were detected to have higher instantaneous speeds during both kiss and run phases compared with the unmutated hTf-endosomes (Fig. 5, C and D). To test our hypothesis of perturbed endosomal cargo affecting the motility of interacting Tf-endosomes, we compared the percentage of frequency distribution of overall hTf- and lock-hTf–endosomal instantaneous speeds, combining those during kiss and run phases. Although the majority of the Tf-endosomes in both cases (hTf and lock-hTf) was found to have an instantaneous speed in the range of 0.2–0.5 µm/s, we noticed that a higher percentage of the lock-hTf–endosomes trafficked at increased instantaneous speeds (>0.5 µm/s) compared with the hTf-endosomes (Fig. 6 A). The mean instantaneous speed of interacting lock-hTf–endosomes at 0.59 µm/s was found to be significantly higher (P < 0.001) than that of the hTf-endosomes at 0.47 µm/s (Fig. 6 B). We then obtained the track speed of each interacting endosome by dividing its track length by its total track time in the time-lapse video. The interacting lock-hTf–endosomes were found to traffic at higher track speeds compared with the interacting hTf-endosomes (Fig. 6 C). The mean track speed of all interacting lock-hTf–endosomes (n = 356) was found to be significantly higher (P < 0.001) than that of the hTf-endosomes (n = 131; Fig. 6 D). The increased motility of interacting lock-hTf compared with hTf-endosomes is strengthened by the absence of any significant differences observed among their total track lengths (Fig. 6, E and F) as well as track displacement lengths (shortest linear distance between the first and last points of the track; Fig. 6 H). Interacting endosomal tracks in representative hTf (Fig. 6 I, enlarged ROIs 1 and 2) and lock-hTf (Fig. 6 J, enlarged ROIs 1 and 2) time-lapses show similar distribution of lengths. These results imply that iron-mediated Tf–TfR conformational changes impact the motility of endosomes that interact with mitochondria.


Endosome – mitochondria interactions are modulated by iron release from transferrin
Lock-hTf–endosomes interacting with mitochondria have increased speeds. (A) Percent frequency distribution of overall instantaneous speeds (during kiss and run phases combined) of interacting hTf-endosomes versus lock-hTf–endosomes indicates that lock-hTf–endosomes have higher motility. (B) The mean instantaneous speed of lock-hTf–endosomes was significantly higher than that of hTf-endosomes. (C) Percent frequency distribution of endosomal track speeds (total length of track divided by time taken to form the track) of interacting hTf-endosomes versus lock-hTf–endosomes also indicate higher speeds for the lock-hTf–endosomes. (D) The mean track speed of the lock-hTf–endosomes was significantly higher than that of the hTf-endosomes. (E and F) The percent frequency distribution of track lengths for hTf- and lock-hTf–endosomes was similar (E), and the difference between their mean track lengths (F) was not statistically significant. (G and H) The percent frequency distribution of track displacement lengths (the shortest linear distance between the starting and ending point of a track) for hTf- and lock-hTf–endosomes was also similar (G), and the difference between their mean values (H) was not statistically significant. Error bars: 95% confidence interval; **, P < 0.001, Student’s t test. (I) Interacting hTf-endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. (J) Interacting lock-hTf–endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. Bars, 10 µm.
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fig6: Lock-hTf–endosomes interacting with mitochondria have increased speeds. (A) Percent frequency distribution of overall instantaneous speeds (during kiss and run phases combined) of interacting hTf-endosomes versus lock-hTf–endosomes indicates that lock-hTf–endosomes have higher motility. (B) The mean instantaneous speed of lock-hTf–endosomes was significantly higher than that of hTf-endosomes. (C) Percent frequency distribution of endosomal track speeds (total length of track divided by time taken to form the track) of interacting hTf-endosomes versus lock-hTf–endosomes also indicate higher speeds for the lock-hTf–endosomes. (D) The mean track speed of the lock-hTf–endosomes was significantly higher than that of the hTf-endosomes. (E and F) The percent frequency distribution of track lengths for hTf- and lock-hTf–endosomes was similar (E), and the difference between their mean track lengths (F) was not statistically significant. (G and H) The percent frequency distribution of track displacement lengths (the shortest linear distance between the starting and ending point of a track) for hTf- and lock-hTf–endosomes was also similar (G), and the difference between their mean values (H) was not statistically significant. Error bars: 95% confidence interval; **, P < 0.001, Student’s t test. (I) Interacting hTf-endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. (J) Interacting lock-hTf–endosomal tracks magnified (ROIs 1 and 2) from a representative time lapse. Bars, 10 µm.
Mentions: Blocking iron release from Tf prevents iron-mediated conformational changes in the Tf–TfR complex (Eckenroth et al., 2011), thus allowing us to test whether an altered cargo conformation affects the motility of Tf-endosomes that interact with mitochondria. Surprisingly, lock-hTf–endosomes interacting with mitochondria were detected to have higher instantaneous speeds during both kiss and run phases compared with the unmutated hTf-endosomes (Fig. 5, C and D). To test our hypothesis of perturbed endosomal cargo affecting the motility of interacting Tf-endosomes, we compared the percentage of frequency distribution of overall hTf- and lock-hTf–endosomal instantaneous speeds, combining those during kiss and run phases. Although the majority of the Tf-endosomes in both cases (hTf and lock-hTf) was found to have an instantaneous speed in the range of 0.2–0.5 µm/s, we noticed that a higher percentage of the lock-hTf–endosomes trafficked at increased instantaneous speeds (>0.5 µm/s) compared with the hTf-endosomes (Fig. 6 A). The mean instantaneous speed of interacting lock-hTf–endosomes at 0.59 µm/s was found to be significantly higher (P < 0.001) than that of the hTf-endosomes at 0.47 µm/s (Fig. 6 B). We then obtained the track speed of each interacting endosome by dividing its track length by its total track time in the time-lapse video. The interacting lock-hTf–endosomes were found to traffic at higher track speeds compared with the interacting hTf-endosomes (Fig. 6 C). The mean track speed of all interacting lock-hTf–endosomes (n = 356) was found to be significantly higher (P < 0.001) than that of the hTf-endosomes (n = 131; Fig. 6 D). The increased motility of interacting lock-hTf compared with hTf-endosomes is strengthened by the absence of any significant differences observed among their total track lengths (Fig. 6, E and F) as well as track displacement lengths (shortest linear distance between the first and last points of the track; Fig. 6 H). Interacting endosomal tracks in representative hTf (Fig. 6 I, enlarged ROIs 1 and 2) and lock-hTf (Fig. 6 J, enlarged ROIs 1 and 2) time-lapses show similar distribution of lengths. These results imply that iron-mediated Tf–TfR conformational changes impact the motility of endosomes that interact with mitochondria.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Using superresolution and quantitative fluorescence microscopy, Das et al. have revealed that iron-transferrin&ndash;containing endosomes directly interact with mitochondria, facilitating iron transfer in epithelial cells. Their findings further enrich the repertoire of organelle&ndash;organelle direct interactions to accomplish a functional significance.

No MeSH data available.