Apaf1 plays a pro-survival role by regulating centrosome morphology and function

Elisabetta Ferraro, Maria Grazia Pesaresi, Daniela De Zio, Maria Teresa Cencioni, Anne Gortat, Mauro Cozzolino, Libera Berghella, Anna Maria Salvatore, Bjorn Oettinghaus, Luca Scorrano, Enrique Pérez-Paya, Francesco Cecconi

Research output: Contribution to journalArticle

Abstract

The apoptotic protease activating factor 1 (Apaf1) is the main component of the apoptosome, and a crucial factor in the mitochondriadependent 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.

Original languageEnglish
Pages (from-to)3450-3463
Number of pages14
JournalJournal of Cell Science
Volume124
Issue number20
DOIs
Publication statusPublished - Oct 2011

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Keywords

  • Apaf1
  • Centrosome
  • Microtubules

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ferraro, E., Pesaresi, M. G., De Zio, D., Cencioni, M. T., Gortat, A., Cozzolino, M., Berghella, L., Salvatore, A. M., Oettinghaus, B., Scorrano, L., Pérez-Paya, E., & Cecconi, F. (2011). Apaf1 plays a pro-survival role by regulating centrosome morphology and function. Journal of Cell Science, 124(20), 3450-3463. https://doi.org/10.1242/jcs.086298