Cytochrome c speeds up caspase cascade activation by blocking 14-3-3¿-dependent Apaf-1 inhibition article

Elena-Real, C.A. ; Díaz-Quintana, A. ; González-Arzola, K. ; Velázquez-Campoy, A. (Universidad de Zaragoza) ; Orzáez, M. ; López-Rivas, A. ; Gil-Caballero, S. ; De La Rosa, M.Á. ; Díaz-Moreno, I.

Resumen: Apoptosis is a highly regulated form of programmed cell death, essential to the development and homeostasis of multicellular organisms. Cytochrome c is a central figure in the activation of the apoptotic intrinsic pathway, thereby activating the caspase cascade through its interaction with Apaf-1. Our recent studies have revealed 14-3-3€ (a direct inhibitor of Apaf-1) as a cytosolic cytochrome c target. Here we explore the cytochrome c / 14-3-3€ interaction and show the ability of cytochrome c to block 14-3-3€-mediated Apaf-1 inhibition, thereby unveiling a novel function for cytochrome c as an indirect activator of caspase-9/3. We have used calorimetry, NMR spectroscopy, site mutagenesis and computational calculations to provide an insight into the structural features of the cytochrome c / 14-3-3€ complex. Overall, these findings suggest an additional cytochrome c-mediated mechanism to modulate apoptosome formation, shedding light onto the rigorous apoptotic regulation network.

Idioma: Inglés

DOI: 10.1038/s41419-018-0408-1

Año: 2018

Publicado en: Cell death & disease 9, 3 (2018), 365 [12 pp]
ISSN: 2041-4889

Factor impacto JCR: 5.959 (2018)

Categ. JCR: CELL BIOLOGY rank: 38 / 191 = 0.199 (2018) - Q1 - T1

Factor impacto SCIMAGO: 2.31 - Cancer Research (Q1) - Cell Biology (Q1) - Medicine (miscellaneous) (Q1) - Immunology (Q1) - Cellular and Molecular Neuroscience (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064P-BMC
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2015-71017-P-BMC
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2015-64383-P

Tipo y forma: Article (Published version)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)