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Artículo del mes 2017

Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48

IIQ

B. Moreno-Beltrán, A. Guerra-Castellano, A. Díaz-Quintana, R. Del Conte, S. M. García-Mauriño, S. Díaz-Moreno, K. González-Arzola, C. Santos-Ocaña, A. Velázquez-Campoy, M.A. De la Rosa, P. Turano, I. Díaz-Moreno. Proceedings of the National Academy of Sciences of the USA 2017, Vol. 0, doi:10.1073/pnas.1618008114

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-methyl- L-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.

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  • Pertenecer a uno de los Institutos del cicCartuja
  • Ser menor de 31 años en el momento de presentar su solicitud
  • Ser el primer firmante del artículo
  • Haberse publicado en los últimos 6 meses
  • El trabajo debe haberse realizado, al menos en parte, en el cicCartuja

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