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Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis.
García-Aguilar, Ana; Martínez-Reyes, Inmaculada; Cuezva, José M.
Affiliation
  • García-Aguilar A; Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER-ISCIII, Instituto de Investigación Hospital 12 de Octubre (i+12) , Universidad Autónoma de Madrid , 28049 Madrid , Spain.
  • Martínez-Reyes I; Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER-ISCIII, Instituto de Investigación Hospital 12 de Octubre (i+12) , Universidad Autónoma de Madrid , 28049 Madrid , Spain.
  • Cuezva JM; Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER-ISCIII, Instituto de Investigación Hospital 12 de Octubre (i+12) , Universidad Autónoma de Madrid , 28049 Madrid , Spain.
J Proteome Res ; 18(8): 3142-3155, 2019 08 02.
Article in En | MEDLINE | ID: mdl-31293153
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteome / Energy Metabolism / Cellular Reprogramming / Proteostasis Limits: Humans Language: En Journal: J Proteome Res Journal subject: BIOQUIMICA Year: 2019 Document type: Article Affiliation country: Spain

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteome / Energy Metabolism / Cellular Reprogramming / Proteostasis Limits: Humans Language: En Journal: J Proteome Res Journal subject: BIOQUIMICA Year: 2019 Document type: Article Affiliation country: Spain