title: Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan.
abstract: Mitochondrial dysfunction has been a hallmark of cancer. However, whether it has a causative role awaits to be elucidated. Here, using an animal model derived from inactivation of SUV3, a mitochondrial helicase, we demonstrated that mSuv3+/- mice harbored increased mitochondrial DNA (mtDNA) mutations and decreased mtDNA copy numbers, leading to tumor development in various sites and shortened lifespan. These phenotypes were transmitted maternally, indicating the etiological role of the mitochondria. Importantly, reduced SUV3 expression was observed in human breast tumor specimens compared with corresponding normal tissues in two independent cohorts. These results demonstrated for the first time that maintaining mtDNA integrity by SUV3 helicase is critical for cancer suppression.
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA. plchen@uci.edu
authors.forename: P-L
authors.initials: PL
authors.lastname: Chen
authors.forename: C-F
authors.initials: CF
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: X E
authors.initials: XE
authors.lastname: Guo
authors.forename: C-K
authors.initials: CK
authors.lastname: Huang
authors.forename: J-Y
authors.initials: JY
authors.lastname: Shew
authors.forename: R L
authors.initials: RL
authors.lastname: Reddick
authors.forename: D C
authors.initials: DC
authors.lastname: Wallace
authors.forename: W-H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D020964:Embryo Loss / Q000235:genetics; D005260:Female; D054629:Genome, Mitochondrial; D042822:Genomic Instability; D057895:Haploinsufficiency; D006579:Heterozygote; D006801:Humans; D008019:Life Style; D008136:Longevity / Q000235:genetics; D051379:Mice
chemical_list: C469673:SUPV3L1 protein, human; D053487:DEAD-box RNA Helicases