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The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR

Author

Listed:
  • Randall M. Chin

    (Molecular Biology Institute, University of California Los Angeles)

  • Xudong Fu

    (University of California Los Angeles)

  • Melody Y. Pai

    (Molecular Biology Institute, University of California Los Angeles)

  • Laurent Vergnes

    (University of California Los Angeles)

  • Heejun Hwang

    (University of California Los Angeles)

  • Gang Deng

    (University of California Los Angeles)

  • Simon Diep

    (University of California Los Angeles)

  • Brett Lomenick

    (University of California Los Angeles)

  • Vijaykumar S. Meli

    (University of California Los Angeles)

  • Gabriela C. Monsalve

    (University of California Los Angeles)

  • Eileen Hu

    (University of California Los Angeles)

  • Stephen A. Whelan

    (University of California Los Angeles)

  • Jennifer X. Wang

    (Small Molecule Mass Spectrometry Facility, Harvard University)

  • Gwanghyun Jung

    (University of California Los Angeles)

  • Gregory M. Solis

    (The Scripps Research Institute)

  • Farbod Fazlollahi

    (Pasarow Mass Spectrometry Laboratory, University of California Los Angeles)

  • Chitrada Kaweeteerawat

    (University of California Los Angeles)

  • Austin Quach

    (University of California Los Angeles)

  • Mahta Nili

    (University of California Los Angeles)

  • Abby S. Krall

    (University of California Los Angeles)

  • Hilary A. Godwin

    (University of California Los Angeles)

  • Helena R. Chang

    (University of California Los Angeles)

  • Kym F. Faull

    (Pasarow Mass Spectrometry Laboratory, University of California Los Angeles)

  • Feng Guo

    (University of California Los Angeles)

  • Meisheng Jiang

    (University of California Los Angeles)

  • Sunia A. Trauger

    (Small Molecule Mass Spectrometry Facility, Harvard University)

  • Alan Saghatelian

    (Harvard University)

  • Daniel Braas

    (University of California Los Angeles
    UCLA Metabolomics Center, University of California Los Angeles)

  • Heather R. Christofk

    (University of California Los Angeles
    UCLA Metabolomics Center, University of California Los Angeles)

  • Catherine F. Clarke

    (Molecular Biology Institute, University of California Los Angeles
    University of California Los Angeles)

  • Michael A. Teitell

    (Molecular Biology Institute, University of California Los Angeles
    University of California Los Angeles)

  • Michael Petrascheck

    (The Scripps Research Institute)

  • Karen Reue

    (Molecular Biology Institute, University of California Los Angeles
    University of California Los Angeles)

  • Michael E. Jung

    (Molecular Biology Institute, University of California Los Angeles
    University of California Los Angeles)

  • Alison R. Frand

    (University of California Los Angeles)

  • Jing Huang

    (Molecular Biology Institute, University of California Los Angeles
    University of California Los Angeles)

Abstract

Ageing in the worm Caenorhabditis elegans is shown to be delayed by supplementation with α-ketoglutarate, an effect that is probably mediated by ATP synthase—which is identified as a direct target of α-ketoglutarate—and target of rapamycin (TOR).

Suggested Citation

  • Randall M. Chin & Xudong Fu & Melody Y. Pai & Laurent Vergnes & Heejun Hwang & Gang Deng & Simon Diep & Brett Lomenick & Vijaykumar S. Meli & Gabriela C. Monsalve & Eileen Hu & Stephen A. Whelan & Jen, 2014. "The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR," Nature, Nature, vol. 510(7505), pages 397-401, June.
  • Handle: RePEc:nat:nature:v:510:y:2014:i:7505:d:10.1038_nature13264
    DOI: 10.1038/nature13264
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    Cited by:

    1. Eunah Kim & Andrea Annibal & Yujin Lee & Hae-Eun H. Park & Seokjin Ham & Dae-Eun Jeong & Younghun Kim & Sangsoon Park & Sujeong Kwon & Yoonji Jung & JiSoo Park & Sieun S. Kim & Adam Antebi & Seung-Jae, 2023. "Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Haibo Wang & Ligang Hu & Hongyan Li & Yau-Tsz Lai & Xueying Wei & Xiaohan Xu & Zhenkun Cao & Huiming Cao & Qianya Wan & Yuen-Yan Chang & Aimin Xu & Qunfang Zhou & Guibin Jiang & Ming-Liang He & Hongzh, 2023. "Mitochondrial ATP synthase as a direct molecular target of chromium(III) to ameliorate hyperglycaemia stress," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Nan Wu & Yi-Cheng Ma & Xin-Qian Gong & Pei-Ji Zhao & Yong-Jian Jia & Qiu Zhao & Jia-Hong Duan & Cheng-Gang Zou, 2023. "The metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Juewon Kim & Yunju Jo & Donghyun Cho & Dongryeol Ryu, 2022. "L-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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