title: Apaf1 plays a pro-survival role by regulating centrosome morphology and function.
abstract: The apoptotic protease activating factor 1 (Apaf1) is the main component of the apoptosome, and a crucial factor in the mitochondria-dependent death pathway. Here we show that Apaf1 plays a role in regulating centrosome maturation. By analyzing Apaf1-depleted cells, we have found that Apaf1 loss induces centrosome defects that impair centrosomal microtubule nucleation and cytoskeleton organization. This, in turn, affects several cellular processes such as mitotic spindle formation, cell migration and mitochondrial network regulation. As a consequence, Apaf1-depleted cells are more fragile and have a lower threshold to stress than wild-type cells. In fact, we found that they exhibit low Bcl-2 and Bcl-X(L) expression and, under apoptotic treatment, rapidly release cytochrome c. We also show that Apaf1 acts by regulating the recruitment of HCA66, with which it interacts, to the centrosome. This function of Apaf1 is carried out during the cell life and is not related to its apoptotic role. Therefore, Apaf1 might also be considered a pro-survival molecule, whose absence impairs cell performance and causes a higher responsiveness to stressful conditions.
authors: Laboratory of Molecular Neuroembryology, IRCCS Fondazione Santa Lucia, 00143, Rome,  Italy.
authors: Elisabetta
authors: E
authors: Ferraro
authors: Maria Grazia
authors: MG
authors: Pesaresi
authors: Daniela
authors: D
authors: De Zio
authors: Maria Teresa
authors: MT
authors: Cencioni
authors: Anne
authors: A
authors: Gortat
authors: Mauro
authors: M
authors: Cozzolino
authors: Libera
authors: L
authors: Berghella
authors: Anna Maria
authors: AM
authors: Salvatore
authors: Bjorn
authors: B
authors: Oettinghaus
authors: Luca
authors: L
authors: Scorrano
authors: Enrique
authors: E
authors: Pérez-Payà
authors: Francesco
authors: F
authors: Cecconi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D002352:Carrier Proteins; C570117:HCA66 protein, mouse