Interaction between AIF and CHCHD4 regulates respiratory chain biogenesis

Hangen, E. et al. (2015) Interaction between AIF and CHCHD4 regulates respiratory chain biogenesis. Molecular Cell, 58(6), pp. 1001-1014. (doi: 10.1016/j.molcel.2015.04.020) (PMID:26004228)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tokatlidis, Professor Kostas and Chatzi, Ms Afroditi and Nuebel, Dr Esther
• Authors: 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., and Modjtahedi, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Molecular Cell
• Publisher: Elsevier Inc.
• ISSN: 1097-2765
• ISSN (Online): 1097-4164
• Published Online: 21 May 2015
• Copyright Holders: Copyright © 2015 Elsevier
• First Published: First published in Molecular Cell 58(6):1001-1014
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher