RT Journal Article
T1 Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
A1 García Aguilar, Ana
A1 Martinez Reyes, Inmaculada
A1 Cuezva, José Manuel
AB 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.
PB American Chemical Society
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/115682
UL https://hdl.handle.net/20.500.14352/115682
LA eng
NO García-Aguilar, A., Martínez-Reyes, I., & Cuezva, J. M. (2019). Changes in the turnover of the cellular proteome during metabolic reprogramming: A role for mtROS in proteostasis. Journal of proteome research, 18(8), 3142-3155.
NO Fundacion Ramoón Areces
NO Ministerio de Economía y Competitividad (España)
NO Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas
DS Docta Complutense
RD 7 abr 2025