Article
Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48
Author/s | Moreno Beltrán, José Blas
Guerra Castellano, Alejandra ![]() ![]() ![]() ![]() ![]() Díaz Quintana, Antonio Jesús ![]() ![]() ![]() ![]() ![]() ![]() ![]() Conte, Rebecca del García Mauriño, Sofía M. González Arzola, Katiuska ![]() ![]() ![]() ![]() ![]() ![]() ![]() Rosa Acosta, Miguel Ángel de la ![]() ![]() ![]() ![]() ![]() ![]() Díaz Moreno, Irene ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
Department | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Publication Date | 2017 |
Deposit Date | 2018-01-02 |
Published in |
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Abstract | 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 ... 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. |
Funding agencies | Ministerio de Economía y Competitividad (MINECO). España European Union (UE) |
Project ID. | BFU2015-71017-P/BMC
![]() BFU2015- 19451/BMC ![]() Bio-NMR-00130 ![]() CALIPSO-312284 ![]() AP2009-4092 ![]() |
Citation | Moreno Beltrán, J.B., Guerra Castellano, A., Díaz Quintana, A., Conte, R.d., García Mauriño, S.M., González Arzola, K.,...,Díaz Moreno, I. (2017). Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48. Proceedings of the National Academy of Sciences, 114 (15), E3041-E3050. |
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