Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
The role played by protein turnover in metabolic reprogramming is unknown. Herein, using a SILAC approach, we have studied the changes in the half-life of 266 proteins of energy metabolism and of translation during the metabolic switch induced by the prolyl hydroxylases inhibitor dimethyloxalylglyci...
| Authors: | ; ; |
|---|---|
| Format: | Article |
| Publication date: | 2019 |
| Country: | España |
| Institution: | Universidad Complutense de Madrid (UCM) |
| Repository: | Docta Complutense |
| Language: | English |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/115682 |
| Online Access: | https://hdl.handle.net/20.500.14352/115682 |
| Access Level: | Open access |
| Keyword: | Biología celular (Farmacia) Biología molecular (Biología) Bioquímica (Farmacia) 2415 Biología Molecular 2407 Biología Celular |
| _version_ | 1878734360545329153 |
|---|---|
| author | García Aguilar, Ana |
| author2 | Martinez Reyes, Inmaculada Cuezva, José Manuel |
| author2_role | author author |
| author_browse | Cuezva, José Manuel García Aguilar, Ana Martinez Reyes, Inmaculada |
| author_facet | García Aguilar, Ana Martinez Reyes, Inmaculada Cuezva, José Manuel |
| author_role | author |
| collection | Docta Complutense |
| description | The role played by protein turnover in metabolic reprogramming is unknown. Herein, using a SILAC approach, we have studied the changes in the half-life of 266 proteins of energy metabolism and of translation during the metabolic switch induced by the prolyl hydroxylases inhibitor dimethyloxalylglycine (DMOG). DMOG induces HIF-1α expression and triggers the activation of glycolysis and the concurrent inhibition of mitochondrial respiration in colon cancer cells. Changes in the activity of energy provision pathways correlated with increased turnover rates of glycolytic enzymes and the stabilization of mitochondrial proteins. Moreover, reprogramming also stabilized the proteins of translation. The partial DMOG-mediated arrest of the synthesis of mitochondrial and translation proteins results from the inhibition of the mTORC1/p70SK/S6 signaling pathway. In contrast, DMOG stimulated the synthesis of glycolytic enzymes, emphasizing the opposite and differential regulation of the two pathways of energy provision. Addition of MitoQ, a mitochondrial reactive oxygen species (mtROS) scavenger, stabilized the turnover of cellular proteins similarly as when protein degradation is inhibited with leupeptin, a serine-protease inhibitor. Overall, the results show that the higher the activity of a pathway the lower is the half-life of the proteins involved and suggest a role for mtROS in cellular proteostasis. Data are available via ProteomeXchange with identifier PXD013482. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_6880b8a2a4dfe322ad817b3c2ae45310 |
| institution | Universidad Complutense de Madrid (UCM) |
| instname_str | Universidad Complutense de Madrid (UCM) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:docta.ucm.es:20.500.14352/115682 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher | American Chemical Society |
| publisherStr | American Chemical Society |
| reponame_str | Docta Complutense |
| spelling | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis García Aguilar, Ana Martinez Reyes, Inmaculada Cuezva, José Manuel Biología celular (Farmacia) Biología molecular (Biología) Bioquímica (Farmacia) 2415 Biología Molecular 2407 Biología Celular The role played by protein turnover in metabolic reprogramming is unknown. Herein, using a SILAC approach, we have studied the changes in the half-life of 266 proteins of energy metabolism and of translation during the metabolic switch induced by the prolyl hydroxylases inhibitor dimethyloxalylglycine (DMOG). DMOG induces HIF-1α expression and triggers the activation of glycolysis and the concurrent inhibition of mitochondrial respiration in colon cancer cells. Changes in the activity of energy provision pathways correlated with increased turnover rates of glycolytic enzymes and the stabilization of mitochondrial proteins. Moreover, reprogramming also stabilized the proteins of translation. The partial DMOG-mediated arrest of the synthesis of mitochondrial and translation proteins results from the inhibition of the mTORC1/p70SK/S6 signaling pathway. In contrast, DMOG stimulated the synthesis of glycolytic enzymes, emphasizing the opposite and differential regulation of the two pathways of energy provision. Addition of MitoQ, a mitochondrial reactive oxygen species (mtROS) scavenger, stabilized the turnover of cellular proteins similarly as when protein degradation is inhibited with leupeptin, a serine-protease inhibitor. Overall, the results show that the higher the activity of a pathway the lower is the half-life of the proteins involved and suggest a role for mtROS in cellular proteostasis. Data are available via ProteomeXchange with identifier PXD013482. American Chemical Society https://hdl.handle.net/20.500.14352/115682 |
| spellingShingle | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis García Aguilar, Ana Biología celular (Farmacia) Biología molecular (Biología) Bioquímica (Farmacia) 2415 Biología Molecular 2407 Biología Celular |
| title | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis |
| title_full | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis |
| title_fullStr | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis |
| title_full_unstemmed | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis |
| title_short | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis |
| title_sort | Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis |
| topic | Biología celular (Farmacia) Biología molecular (Biología) Bioquímica (Farmacia) 2415 Biología Molecular 2407 Biología Celular |
| topic_facet | Biología celular (Farmacia) Biología molecular (Biología) Bioquímica (Farmacia) 2415 Biología Molecular 2407 Biología Celular |
| url | https://hdl.handle.net/20.500.14352/115682 |