Details

Autor(en) / Beteiligte

• Hangen, Emilie
• Féraud, Olivier
• Lachkar, Sylvie
• Mou, Haiwei
• Doti, Nunzianna
• Fimia, Gian Maria
• Lam, Ngoc-vy
• Zhu, Changlian
• Godin, Isabelle
• Muller, Kevin
• Chatzi, Afroditi
• Nuebel, Esther
• Ciccosanti, Fabiola
• Flamant, Stéphane
• Bénit, Paule
• Perfettini, Jean-Luc
• Sauvat, Allan
• Bennaceur-Griscelli, Annelise
• Ser-Le Roux, Karine
• Gonin, Patrick
• Tokatlidis, Kostas
• Rustin, Pierre
• Piacentini, Mauro
• Ruvo, Menotti
• Blomgren, Klas
• Kroemer, Guido
• Modjtahedi, Nazanine

Titel

Interaction between AIF and CHCHD4 Regulates Respiratory Chain Biogenesis

Ist Teil von

• Molecular cell, 2015-06, Vol.58 (6), p.1001-1014

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •AIF interacts with CHCHD4, a regulator of the intermembrane space import machinery•AIF regulates specific respiratory chain complexes by acting upstream of CHCHD4•AIF is indispensable for translation-coupled mitochondrial import of CHCHD4•Restoring CHCHD4 reverses the metabolic and cell death phenotypes of Aif−/y ESCs Hangen et al. show that the mitochondrial protein AIF regulates the biogenesis of respiratory chain complexes by interacting with, and by controlling the mitochondrial import of the mammalian homolog of yeast MIA40, CHCHD4, which is the central component of a redox-sensitive mitochondrial intermembrane space import machinery.