Peroxisomicine A1 (PA1) is a potential antineoplastic agent with high and selective toxicity toward peroxisomes of tumor cells. Pexophagy is a selective autophagy process that degrades damaged peroxisomes; this process has been studied mainly in methylotrophic yeasts. There are two main modes of pexophagy in yeast: macropexophagy and micropexophagy. Previous studies showed that peroxisomes damaged by a prolonged exposition to PA1 are eliminated by macropexophagy. In this work, Candida boidinii was grown in methanol‐containing media, and PA1 was added to the cultures at 2 µg/mL after they reached the mid‐exponential growth phase. Samples were taken at 5, 10, 15, 20, and 25 min after the addition of PA1 and processed for ultrastructural analysis. Typical morphological characteristics of micropexophagy were observed: the direct engulfment of peroxisomes by the vacuolar membrane and the presence of the micropexophagic membrane apparatus (MIPA), which mediates the fusion between the opposing tips of the vacuole to complete sequestration of peroxisomes from the cytosol. In conclusion, here we report that, in addition to macropexophagy, peroxisomes damaged by PA1 can be eliminated by micropexophagy. This information is useful to deepen the knowledge of the mechanism of action of PA1 and of that of pexophagy per se.
The cover image is based on the Short Communication Peroxisomicine A1, a potential antineoplastic agent, causes micropexophagy in addition to macropexophagy by Gilberto Jaramillo‐Rangel, Juan Solis‐Soto, Alberto Niderhauser‐Garcia et al., https://doi.org/10.1002/cbin.11280.
<b><i>Introduction:</i></b> The diameter and area of the proximal convoluted tubule (PCT) and the distal convoluted tubule (DCT) are of the main parameters analyzed in stereological studies of the kidney. However, there is no consensus about if the PCT and DCT should be considered circular or elliptical in shape. <b><i>Objective:</i></b> To analyze if there are significant differences in the diameter and area of the PCT and DCT, depending on whether they are considered circular or elliptical. <b><i>Methods:</i></b> Paraffin-embedded sections of kidneys from CD1 mice were stained with hematoxylin and eosin and examined using a light microscope. Images were captured using a camera linked to image analysis software. A short diameter (<i>d</i>) and a long diameter (<i>D</i>) were measured in both PCT and DCT. A small circular area (SCA), a large circular area (LCA), and an elliptical area (EA) were calculated with mathematical formulas that incorporate <i>d</i> and <i>D</i> values, while a program area (PA) was provided by the software. <b><i>Results:</i></b> There was a significant difference between <i>d</i> and <i>D</i> in both PCT (<i>F</i> = 1.354, Sig = 0.000) and DCT (<i>F</i> = 4.989, Sig = 0.000). Also, there were significant differences in the tubular areas in both PCT (<i>F</i> = 34.843, Sig = 0.000) and DCT (<i>F</i> = 22.390, Sig = 0.000); circular areas were different from elliptical areas (SCA and LCA vs. EA and PA). <b><i>Conclusion:</i></b> The convoluted tubules of the nephron must not be considered circular, but rather elliptical; care should be taken every time the tubules are analyzed in stereological studies of the kidney, especially when evaluating their diameters and areas.
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