| Autor: |
Moreno-Beltrán, Blas, Guerra-Castellano, Alejandra, Díaz-Quintana, Antonio, Del Conte, Rebecca, García-Mauriño, Sofía M., Díaz-Moreno, Sofía, González-Arzola, Katiuska, Santos-Ocaña, Carlos, Velázquez-Campoy, Adrián, De la Rosa, Miguel A., Turano, Paola, Díaz-Moreno, Irene |
| Rok vydání: |
2017 |
| Popis: |
Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation—in particular, at tyrosine 48—is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methylL-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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