Fancd2 in vivo interaction network reveals a non-canonical role in mitochondrial function

Sci Rep. 2017 Apr 5;7:45626. doi: 10.1038/srep45626.

Abstract

Fancd2 is a component of the Fanconi anemia (FA) DNA repair pathway, which is frequently found defective in human cancers. The full repertoire of Fancd2 functions in normal development and tumorigenesis remains to be determined. Here we developed a Flag- and hemagglutinin-tagged Fancd2 knock-in mouse strain that allowed a high throughput mass spectrometry approach to search for Fancd2-binding proteins in different mouse organs. In addition to DNA repair partners, we observed that many Fancd2-interacting proteins are mitochondrion-specific. Fancd2 localizes in the mitochondrion and associates with the nucleoid complex components Atad3 and Tufm. The Atad3-Tufm complex is disrupted in Fancd2-/- mice and those deficient for the FA core component Fanca. Fancd2 mitochondrial localization requires Atad3. Collectively, these findings provide evidence for Fancd2 as a crucial regulator of mitochondrion biosynthesis, and of a molecular link between FA and mitochondrial homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Animals
  • Fanconi Anemia Complementation Group D2 Protein / metabolism*
  • Gene Knock-In Techniques
  • Mass Spectrometry
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Peptide Elongation Factor Tu / metabolism*
  • Protein Binding
  • Protein Interaction Maps*

Substances

  • Atad3a protein, mouse
  • Fancd2 protein, mouse
  • Fanconi Anemia Complementation Group D2 Protein
  • Mitochondrial Proteins
  • Peptide Elongation Factor Tu
  • Tufm protein, mouse
  • ATPases Associated with Diverse Cellular Activities