Mitochondrial nucleoid trafficking regulated by the inner-membrane AAA-ATPase ATAD3A modulates respiratory complex formation

Proc Natl Acad Sci U S A. 2022 Nov 22;119(47):e2210730119. doi: 10.1073/pnas.2210730119. Epub 2022 Nov 16.


Mitochondria have their own DNA (mtDNA), which encodes essential respiratory subunits. Under live imaging, mitochondrial nucleoids, composed of several copies of mtDNA and DNA-binding proteins, such as mitochondrial transcription factor A (TFAM), actively move inside mitochondria and change the morphology, in concert with mitochondrial membrane fission. Here we found the mitochondrial inner membrane-anchored AAA-ATPase protein ATAD3A mediates the nucleoid dynamics. Its ATPase domain exposed to the matrix binds directly to TFAM and mediates nucleoid trafficking along mitochondria by ATP hydrolysis. Nucleoid trafficking also required ATAD3A oligomerization via an interaction between the coiled-coil domains in intermembrane space. In ATAD3A deficiency, impaired nucleoid trafficking repressed the clustered and enlarged nucleoids observed in mitochondrial fission-deficient cells resulted in dispersed distribution of small nucleoids observed throughout the mitochondrial network, and this enhanced respiratory complex formation. Thus, mitochondrial fission and nucleoid trafficking cooperatively determine the size, number, and distribution of nucleoids in mitochondrial network, which should modulate respiratory complex formation.

Keywords: ATAD3A; Drp1; mitochondrial fission; mtDNA nucleoid; respiratory complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • DNA, Mitochondrial / genetics
  • Mitochondria* / metabolism
  • Mitochondrial Dynamics / genetics
  • Mitochondrial Proteins* / genetics
  • Mitochondrial Proteins* / metabolism


  • ATPases Associated with Diverse Cellular Activities
  • Mitochondrial Proteins
  • DNA, Mitochondrial