TTC19 Plays a Husbandry Role on UQCRFS1 Turnover in the Biogenesis of Mitochondrial Respiratory Complex III

Emanuela Bottani, Raffaele Cerutti, Michael E. Harbour, Sabrina Ravaglia, Sukru Anil Dogan, Carla Giordano, Ian M. Fearnley, Giulia D'Amati, Carlo Viscomi, Erika Fernandez-Vizarra, Massimo Zeviani

Research output: Contribution to journalArticlepeer-review


Loss-of-function mutations in TTC19 (tetra-tricopeptide repeat domain 19) have been associated with severe neurological phenotypes and mitochondrial respiratory chain complex III deficiency. We previously demonstrated the mitochondrial localization of TTC19 and its link with complex III biogenesis. Here we provide detailed insight into the mechanistic role of TTC19, by investigating a Ttc19−/− mouse model that shows progressive neurological and metabolic decline decreased complex III activity and increased production of reactive oxygen species. By using both the Ttc19−/− mouse model and a range of human cell lines we demonstrate that TTC19 binds to the fully assembled complex III dimer i.e. after the incorporation of the iron-sulfur Rieske protein (UQCRFS1). The in situ maturation of UQCRFS1 produces N-terminal polypeptides which remain bound to holocomplex III. We show that in normal conditions these UQCRFS1 fragments are rapidly removed but when TTC19 is absent they accumulate within complex III causing its structural and functional impairment.

Original languageEnglish
Pages (from-to)96-105.e4
JournalMolecular Cell
Issue number1
Publication statusPublished - Jul 6 2017


  • complex III deficiency
  • mitochondrial complex III
  • mitochondrial disease
  • mitochondrial quality control
  • mitochondrial respiratory chain
  • mouse model
  • Rieske protein
  • TTC19

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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