Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis
|Author||Martínez Fábregas, Jonathan
Díaz Moreno, Irene
González Arzola, Katiuska
Navarro Carruesco, José Antonio
Hervás Morón, Manuel
Velázquez Campoy, Adrián
Díaz Quintana, Antonio Jesús
Rosa Acosta, Miguel Ángel de la
|Department||Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular|
|Published in||Molecular and Cellular Proteomics, 13 (6), 1439-1456.|
|Abstract||Since the first description of apoptosis four decades ago, great efforts have been made to elucidate, both in vivo and in vitro, the molecular mechanisms involved in its regulation. Although the role of cytochrome c during ...
Since the first description of apoptosis four decades ago, great efforts have been made to elucidate, both in vivo and in vitro, the molecular mechanisms involved in its regulation. Although the role of cytochrome c during apoptosis is well-established, relatively little is known about its participation in signaling pathways in vivo due to its essential role during respiration. To better understand the role of cytochrome c in the onset of apoptosis, a proteomic approach based on affinity chromatography with cytochrome c as bait was used in this study. In this approach, novel cytochrome c interaction partners were identified whose in vivo interaction, as well as cellular localization, were facilitated through bimolecular fluorescence complementation. Modeling of the complexes interface between cytochrome c and its counterparts indicated the involvement of the surface surrounding the heme crevice of cytochrome c, in agreement with the vast majority of known redox adducts of cytochrome c. However, in contrast to the high turnover rate of the mitochondrial cytochrome c redox adducts, those occurring under apoptosis lead to the formation of stable nucleo-cytoplasmic ensembles, as inferred mainly from surface plasmon resonance and nuclear magnetic resonance measurements, which have permitted us to corroborate the formation of such complexes in vitro. The results obtained suggest that human cytochrome c interacts with pro-survival, anti-apoptotic proteins following its release into the cytoplasm. Thus, cytochrome c may interfere with cell survival pathways and unlock apoptosis in order to prevent the spatial and temporal co-existence of antagonist signals.
|Cite||Martínez Fábregas, J., Díaz Moreno, I., González Arzola, K., Janocha, S., Navarro Carruesco, J.A., Hervás Morón, M.,...,Rosa Acosta, M.Á.d.l. (2014). Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis. Molecular and Cellular Proteomics, 13 (6), 1439-1456.|