The AAA+ protein ATAD3 has displacement loop binding properties and is involved in mitochondrial nucleoid organization.

TitleThe AAA+ protein ATAD3 has displacement loop binding properties and is involved in mitochondrial nucleoid organization.
Publication TypeJournal Article
Year of Publication2007
AuthorsHe, J, Mao, C-C, Reyes, A, Sembongi, H, Di Re, M, Granycome, C, Clippingdale, AB, Fearnley, IM, Harbour, M, Robinson, AJ, Reichelt, S, Spelbrink, JN, Walker, JE, Holt, IJ
JournalJ Cell Biol
Date Published2007 Jan 15
KeywordsAdenosine Triphosphatases, Adenosine Triphosphate, Animals, ATPases Associated with Diverse Cellular Activities, Binding Sites, Binding, Competitive, Cell Line, Tumor, DNA, Mitochondrial, DNA, Single-Stranded, DNA, Superhelical, DNA-Binding Proteins, Electrophoresis, Gel, Two-Dimensional, Electrophoretic Mobility Shift Assay, Humans, Membrane Proteins, Mitochondria, Liver, Mitochondrial Proteins, Nucleic Acid Conformation, Nucleoproteins, Peptide Fragments, Plasmids, Protein Binding, Rats, RNA, Small Interfering, Submitochondrial Particles

Many copies of mammalian mitochondrial DNA contain a short triple-stranded region, or displacement loop (D-loop), in the major noncoding region. In the 35 years since their discovery, no function has been assigned to mitochondrial D-loops. We purified mitochondrial nucleoprotein complexes from rat liver and identified a previously uncharacterized protein, ATAD3p. Localization studies suggested that human ATAD3 is a component of many, but not all, mitochondrial nucleoids. Gene silencing of ATAD3 by RNA interference altered the structure of mitochondrial nucleoids and led to the dissociation of mitochondrial DNA fragments held together by protein, specifically, ones containing the D-loop region. In vitro, a recombinant fragment of ATAD3p bound to supercoiled DNA molecules that contained a synthetic D-loop, with a marked preference over partially relaxed molecules with a D-loop or supercoiled DNA circles. These results suggest that mitochondrial D-loops serve to recruit ATAD3p for the purpose of forming or segregating mitochondrial nucleoids.

Alternate JournalJ. Cell Biol.
Citation Key10.1083/jcb.200609158
PubMed ID17210950
PubMed Central IDPMC2063933
Grant ListMC_U105663140 / / Medical Research Council / United Kingdom
MC_U105663148 / / Medical Research Council / United Kingdom
MC_U105674181 / / Medical Research Council / United Kingdom