Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation
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-resourc...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/10/11/1553 |
| _version_ | 1797547908651810816 |
|---|---|
| author | Fahd Boutouja Harald W. Platta |
| author_facet | Fahd Boutouja Harald W. Platta |
| author_sort | Fahd Boutouja |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:50:47Z |
| format | Article |
| id | doaj.art-5f811f9eacab4af8a793f38b8cfd4871 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T14:50:47Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5f811f9eacab4af8a793f38b8cfd48712023-11-20T20:59:21ZengMDPI AGBiomolecules2218-273X2020-11-011011155310.3390/biom10111553Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome DegradationFahd Boutouja0Harald W. Platta1Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, 44801 Bochum, GermanyBiochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, 44801 Bochum, GermanyThe 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.https://www.mdpi.com/2218-273X/10/11/1553autophagyperoxisomespexophagyrapamycinmTORRas2 |
| spellingShingle | Fahd Boutouja Harald W. Platta Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation Biomolecules autophagy peroxisomes pexophagy rapamycin mTOR Ras2 |
| title | Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation |
| title_full | Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation |
| title_fullStr | Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation |
| title_full_unstemmed | Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation |
| title_short | Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation |
| title_sort | autophagy stimulus dependent role of the small gtpase ras2 in peroxisome degradation |
| topic | autophagy peroxisomes pexophagy rapamycin mTOR Ras2 |
| url | https://www.mdpi.com/2218-273X/10/11/1553 |
| work_keys_str_mv | AT fahdboutouja autophagystimulusdependentroleofthesmallgtpaseras2inperoxisomedegradation AT haraldwplatta autophagystimulusdependentroleofthesmallgtpaseras2inperoxisomedegradation |