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Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation

1
Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, 44801 Bochum, Germany
2
Institute of Pathobiochemistry, Johannes Gutenberg-University Mainz, 55099 Mainz, Germany
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(11), 1553; https://doi.org/10.3390/biom10111553
Received: 17 October 2020 / Revised: 7 November 2020 / Accepted: 12 November 2020 / Published: 14 November 2020
(This article belongs to the Section Cellular Biochemistry)
The changing accessibility of nutrient resources induces the reprogramming of cellular metabolism in order to adapt the cell to the altered growth conditions. The nutrient-depending signaling depends on the kinases mTOR (mechanistic target of rapamycin), which is mainly activated by nitrogen-resources, and PKA (protein kinase A), which is mainly activated by glucose, as well as both of their associated factors. These systems promote protein synthesis and cell proliferation, while they inhibit degradation of cellular content by unselective bulk autophagy. Much less is known about their role in selective autophagy pathways, which have a more regulated cellular function. Especially, we were interested to analyse the central Ras2-module of the PKA-pathway in the context of peroxisome degradation. Yeast Ras2 is homologous to the mammalian Ras proteins, whose mutant forms are responsible for 33% of human cancers. In the present study, we were able to demonstrate a context-dependent role of Ras2 activity depending on the type of mTOR-inhibition and glucose-sensing situation. When mTOR was inhibited directly via the macrolide rapamycin, peroxisome degradation was still partially suppressed by Ras2, while inactivation of Ras2 resulted in an enhanced degradation of peroxisomes, suggesting a role of Ras2 in the inhibition of peroxisome degradation in glucose-grown cells. In contrast, the inhibition of mTOR by shifting cells from oleate-medium, which lacks glucose, to pexophagy-medium, which contains glucose and is limited in nitrogen, required Ras2-activity for efficient pexophagy, strongly suggesting that the role of Ras2 in glucose sensing-associated signaling is more important in this context than its co-function in mTOR-related autophagy-inhibition. View Full-Text
Keywords: autophagy; peroxisomes; pexophagy; rapamycin; mTOR; Ras2 autophagy; peroxisomes; pexophagy; rapamycin; mTOR; Ras2
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MDPI and ACS Style

Boutouja, F.; Platta, H.W. Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation. Biomolecules 2020, 10, 1553. https://doi.org/10.3390/biom10111553

AMA Style

Boutouja F, Platta HW. Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation. Biomolecules. 2020; 10(11):1553. https://doi.org/10.3390/biom10111553

Chicago/Turabian Style

Boutouja, Fahd, and Harald W. Platta. 2020. "Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation" Biomolecules 10, no. 11: 1553. https://doi.org/10.3390/biom10111553

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