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Fig. 4 | Journal of Neuroinflammation

Fig. 4

From: Mitochondrial damage and “plugging” of transport selectively in myelinated, small-diameter axons are major early events in peripheral neuroinflammation

Fig. 4

Mitochondria damaged by photo-bleaching remain at the site of damage obstructing the passage of cargoes along the small-diameter axons, resulting in a selective block of transport in small-diameter fibers. Before the photo-bleaching (a), axonal mitochondria appear healthy or electrically polarized (i.e., they fluoresce red, TMRM+), appearing pale/white when they overlap with the blue fluorescence of CFP+ mitochondria. Photo-bleaching induces fragmentation and damage of mitochondria (blue arrows, bd) which remain at the site of damage for over 2 h (e). Depletion of functional mitochondria from the photo-bleached segment of axons induces a compensatory increase in anterograde mitochondrial transport proximal to the bleached site, resulting in re-population of these segments with healthy (TMRM+; red arrows, ce) mitochondria. This mechanism successfully replenishes the mitochondria in axons of large and medium diameter (white asterisks, a, e). However, in small axons, the damaged mitochondria appear to block the passage of healthy mitochondria, resulting in proximal mitochondrial accumulations (white arrows in d, white arrowheads in e), and paucity of healthy mitochondria distal to the transport block—note the lack of TMRM+ mitochondria distal to white arrows, while CFP+ mitochondria remain stationary. Average diameter (±SD) of the fibers with mitochondrial transport block 2.5 h after bleaching was 3.02 (± 0.7) μm (n = 18 axons from three separate experiments)

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