title: RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity.
abstract: RECQL4 is associated with Rothmund-Thomson Syndrome (RTS), a rare autosomal recessive disorder characterized by premature aging, genomic instability, and cancer predisposition. RECQL4 is a member of the RecQ helicase family, and has many similarities to WRN protein, which is also implicated in premature aging. There is no information about whether any of the RecQ helicases play roles in mitochondrial biogenesis, which is strongly implicated in the aging process. Here, we used microscopy to visualize RECQL4 in mitochondria. Fractionation of human and mouse cells also showed that RECQL4 was present in mitochondria. Q-PCR amplification of mitochondrial DNA demonstrated that mtDNA damage accumulated in RECQL4-deficient cells. Microarray analysis suggested that mitochondrial bioenergetic pathways might be affected in RTS. Measurements of mitochondrial bioenergetics showed a reduction in the mitochondrial reserve capacity after lentiviral knockdown of RECQL4 in two different primary cell lines. Additionally, biochemical assays with RECQL4, mitochondrial transcription factor A, and mitochondrial DNA polymerase γ showed that the polymerase inhibited RECQL4's helicase activity. RECQL4 is the first 3'-5' RecQ helicase to be found in both human and mouse mitochondria, and the loss of RECQL4 alters mitochondrial integrity.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Croteau
authors.forename: Marie L
authors.initials: ML
authors.lastname: Rossi
authors.forename: Chandrika
authors.initials: C
authors.lastname: Canugovi
authors.forename: Jane
authors.initials: J
authors.lastname: Tian
authors.forename: Peter
authors.initials: P
authors.lastname: Sykora
authors.forename: Mahesh
authors.initials: M
authors.lastname: Ramamoorthy
authors.forename: Zheng Ming
authors.initials: ZM
authors.lastname: Wang
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Singh
authors.forename: Mansour
authors.initials: M
authors.lastname: Akbari
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kasiviswanathan
authors.forename: William C
authors.initials: WC
authors.lastname: Copeland
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D000818:Animals; D002458:Cell Fractionation / Q000379:methods; D045744:Cell Line, Tumor; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; C506731:RECQL4 protein, human; D053484:RecQ Helicases