Liyanage Sanduni U, Coyaud Etienne, Laurent Estelle M N, Hurren Rose, Maclean Neil, Wood Stuart R, Kazak Lawrence, Shamas-Din Aisha, Holt Ian, Raught Brian, Schimmer Aaron
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, ON, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Mitochondrion. 2017 Jan;32:31-35. doi: 10.1016/j.mito.2016.11.001. Epub 2016 Nov 11.
Human mitochondrial DNA (mtDNA) is replicated by the mitochondrial DNA polymerase gamma (POLG). Using proximity dependent biotin labelling (BioID), we characterized the POLG interactome and identified new interaction partners involved in mtDNA maintenance, transcription, translation and protein quality control. We also identified interaction with the nuclear AAA+ ATPase Ruvbl2, suggesting mitochondrial localization for this protein. Ruvbl2 was detected in mitochondria-enriched fractions in leukemic cells. Additionally, transgenic overexpression of Ruvbl2 from an alternative translation initiation site resulted in mitochondrial co-localization. Overall, POLG interactome mapping identifies novel proteins which support mitochondrial biogenesis and a potential novel mitochondrial isoform of Ruvbl2.
人类线粒体DNA(mtDNA)由线粒体DNA聚合酶γ(POLG)进行复制。我们利用邻近依赖性生物素标记(BioID)技术对POLG相互作用组进行了表征,并鉴定出参与mtDNA维持、转录、翻译及蛋白质质量控制的新相互作用伙伴。我们还发现了POLG与核AAA+ ATP酶Ruvbl2之间的相互作用,提示该蛋白定位于线粒体。在白血病细胞富含线粒体的组分中检测到了Ruvbl2。此外,从一个替代翻译起始位点对Ruvbl2进行转基因过表达导致其与线粒体共定位。总体而言,POLG相互作用组图谱鉴定出了支持线粒体生物发生的新蛋白以及Ruvbl2一种潜在的新线粒体异构体。