title: Altered mitochondria morphology and cell metabolism in Apaf1-deficient cells.
abstract: BACKGROUND
  Apaf1 (apoptotic protease activating factor 1) is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. Other cellular roles, including a pro-survival role, have also been described for Apaf1, while the relative contribution of each function to cell death, but also to cell homeostatic conditions, remain to be clarified.
  
  
  RESULTS
  Here we examined the response to apoptosis induction of available embryonic fibroblasts from Apaf1 knockout mice (MEFS KO Apaf1). In the absence of Apaf1, cells showed mitochondria with an altered morphology that affects cytochrome c release and basal metabolic status.
  
  
  CONCLUSIONS
  We analysed mitochondrial features and cell death response to etoposide and ABT-737 in two different Apaf1-deficient MEFS, which differ in the immortalisation protocol. Unexpectedly, MEFS KO Apaf1 immortalised with the SV40 antigen (SV40IM-MEFS Apaf1) and those which spontaneously immortalised (SIM-MEFS Apaf1) respond differently to apoptotic stimuli, but both presented relevant differences at the mitochondria when compared to MEFS WT, indicating a role for Apaf1 at the mitochondria.
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Sancho
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Gortat
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Herrera
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Andreu-Fernández
authors.affiliation: Laboratory of Skeletal Muscle Development and Metabolism, IRCCS San Raffaele Pisana Institute, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferraro
authors.affiliation: Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, Rome, Italy ; Dulbecco Telethon Institute, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain ; Instituto de Biomedicina de Valencia, IBV-CSIC, Valencia, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Payá
mesh_terms: D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1 / Q000172:deficiency* / Q000235:genetics; D001481:Basal Metabolism; D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*
chemical_list: C506592:APAF1 protein, human; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D045304:Cytochromes c