Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis

Nucleic Acids Res. 2012 Jul;40(13):6109-21. doi: 10.1093/nar/gks266. Epub 2012 Mar 26.

Abstract

Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

Publication types

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

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / metabolism
  • Cell Cycle Proteins / physiology
  • Cell Line, Tumor
  • DNA, Mitochondrial / metabolism
  • HEK293 Cells
  • Humans
  • Membrane Proteins / metabolism
  • Mitochondria / genetics*
  • Mitochondrial Proteins / biosynthesis*
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Proteins / physiology
  • Nuclear Proteins / physiology
  • Nucleoproteins / physiology*
  • Prohibitins
  • Protein Biosynthesis*
  • RNA / analysis
  • RNA / isolation & purification
  • RNA, Messenger / analysis
  • RNA, Mitochondrial
  • Repressor Proteins / physiology
  • Ribosomes / metabolism

Substances

  • ATAD3A protein, human
  • ATAD3B protein, human
  • Cell Cycle Proteins
  • DNA, Mitochondrial
  • GADD45GIP1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Nuclear Proteins
  • Nucleoproteins
  • Prohibitins
  • RNA, Messenger
  • RNA, Mitochondrial
  • Repressor Proteins
  • RNA
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities