• Open Access

RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity

Authors

  • Deborah L. Croteau,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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  • Marie L. Rossi,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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    • These two authors contributed equally to this work.

  • Chandrika Canugovi,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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    • These two authors contributed equally to this work.

  • Jane Tian,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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  • Peter Sykora,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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  • Mahesh Ramamoorthy,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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  • ZhengMing Wang,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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    • Present address: Building 10, Magnuson Clinical Center, Rm 11N112, 10 Center Dr., Bethesda, MD 20892, USA.

  • Dharmendra Kumar Singh,

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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  • Mansour Akbari,

    1. Center for Healthy Aging, SUND, University of Copenhagen, Denmark
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  • Rajesh Kasiviswanathan,

    1. Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
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  • William C. Copeland,

    1. Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
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  • Vilhelm A. Bohr

    1. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA
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Vilhelm A. Bohr, Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 251 Bayview Blvd, Suite 100, Rm 06B133, Baltimore, MD 21224, USA. Tel.: 410 558 8162; fax: 410 558 8157; e-mail: vbohr@nih.gov

Summary

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.

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