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SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation

Author

Listed:
  • Matthew D. Hirschey

    (Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
    University of California, San Francisco, California 94143, USA)

  • Tadahiro Shimazu

    (Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
    University of California, San Francisco, California 94143, USA)

  • Eric Goetzman

    (The Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201, USA)

  • Enxuan Jing

    (Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA)

  • Bjoern Schwer

    (Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
    University of California, San Francisco, California 94143, USA
    Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, The Children’s Hospital, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • David B. Lombard

    (Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, The Children’s Hospital, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Carrie A. Grueter

    (Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA)

  • Charles Harris

    (Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA)

  • Sudha Biddinger

    (Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA)

  • Olga R. Ilkayeva

    (Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27704, USA)

  • Robert D. Stevens

    (Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27704, USA)

  • Yu Li

    (Cell Signaling Technology, Danvers, Massachusetts 01923, USA)

  • Asish K. Saha

    (Physiology, and Biophysics and the Diabetes Unit, Boston University Medical Center, Boston, Massachusetts 02118, USA)

  • Neil B. Ruderman

    (Physiology, and Biophysics and the Diabetes Unit, Boston University Medical Center, Boston, Massachusetts 02118, USA)

  • James R. Bain

    (Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27704, USA)

  • Christopher B. Newgard

    (Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27704, USA)

  • Robert V. Farese Jr

    (Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA)

  • Frederick W. Alt

    (Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, The Children’s Hospital, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • C. Ronald Kahn

    (Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA)

  • Eric Verdin

    (Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
    University of California, San Francisco, California 94143, USA)

Abstract

SIRT3 regulation of fatty acid oxidation The sirtuin family of regulatory proteins has been implicated in various biological pathways including responses to calorie restriction and metabolic stress. Work in mice now shows that sirtuin 3 (SIRT3), which mediates deacetylation of several mitochondrial proteins, is induced in liver and brown adipose tissue during fasting. One of SIRT3's substrates is shown to be long-chain acyl co-enzyme A dehydrogenase (LCAD). Without SIRT3, LCAD becomes hyperacetylated, which diminishes its activity, and reduces fatty acid oxidation. Mice without SIRT3 have all the hallmarks of fatty acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold. These findings suggest that acetylation is a novel regulatory mechanism for fatty acid oxidation.

Suggested Citation

  • Matthew D. Hirschey & Tadahiro Shimazu & Eric Goetzman & Enxuan Jing & Bjoern Schwer & David B. Lombard & Carrie A. Grueter & Charles Harris & Sudha Biddinger & Olga R. Ilkayeva & Robert D. Stevens & , 2010. "SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation," Nature, Nature, vol. 464(7285), pages 121-125, March.
    • Handle: RePEc:nat:nature:v:464:y:2010:i:7285:d:10.1038_nature08778
    DOI: 10.1038/nature08778
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    Cited by:

    1. Diego Sáenz de Urturi & Xabier Buqué & Begoña Porteiro & Cintia Folgueira & Alfonso Mora & Teresa C. Delgado & Endika Prieto-Fernández & Paula Olaizola & Beatriz Gómez-Santos & Maider Apodaka-Biguri &, 2022. "Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Gloria Ursino & Giorgio Ramadori & Anna Höfler & Soline Odouard & Pryscila D. S. Teixeira & Florian Visentin & Christelle Veyrat-Durebex & Giulia Lucibello & Raquel Firnkes & Serena Ricci & Claudia R., 2022. "Hepatic non-parenchymal S100A9-TLR4-mTORC1 axis normalizes diabetic ketogenesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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