Abstract

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that, beyond its apoptotic function, is required for the normal expression of major respiratory chain complexes. Here we identified an AIF-interacting protein, CHCHD4, which is the central component of a redox-sensitive mitochondrial intermembrane space import machinery. Depletion or hypomorphic mutation of AIF caused a downregulation of CHCHD4 protein by diminishing its mitochondrial import. CHCHD4 depletion sufficed to induce a respiratory defect that mimicked that observed in AIF-deficient cells. CHCHD4 levels could be restored in AIF-deficient cells by enforcing its AIF-independent mitochondrial localization. This modified CHCHD4 protein reestablished respiratory function in AIF-deficient cells and enabled AIF-deficient embryoid bodies to undergo cavitation, a process of programmed cell death required for embryonic morphogenesis. These findings explain how AIF contributes to the biogenesis of respiratory chain complexes, and they establish an unexpected link between the vital function of AIF and the propensity of cells to undergo apoptosis.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Hangen E. , Féraud O. , Lachkar S. , Mou H. , Doti N. , Fimia G.M. , Lam N.V. , Zhu C. , Godin I. , Muller K. , Chatzi A. , Nuebel E. , Ciccosanti F. , Flamant S. , Bénit P. , Perfettini J.L. , Sauvat A. , Bennaceur-Griscelli A. , Ser-Le Roux K. , Gonin P. , Tokatlidis K. , Rustin P. , Piacentini M. , Ruvo M. , Blomgren K. , Kroemer G. , Modjtahedi N.

Titolo volume/Rivista

MOLECULAR CELL

Anno di pubblicazione

2015

ISSN

1097-2765

ISBN

Non Disponibile

Numero di citazioni Wos

35

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

38

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile