IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v571y2019i7766d10.1038_s41586-019-1400-3.html
   My bibliography  Save this article

H+ transport is an integral function of the mitochondrial ADP/ATP carrier

Author

Listed:
  • Ambre M. Bertholet

    (University of California San Francisco)

  • Edward T. Chouchani

    (Harvard Medical School)

  • Lawrence Kazak

    (Harvard Medical School)

  • Alessia Angelin

    (University of Pennsylvania)

  • Andriy Fedorenko

    (University of California San Francisco)

  • Jonathan Z. Long

    (Harvard Medical School)

  • Sara Vidoni

    (Harvard Medical School)

  • Ryan Garrity

    (Harvard Medical School)

  • Joonseok Cho

    (University of Florida College of Medicine)

  • Naohiro Terada

    (University of Florida College of Medicine)

  • Douglas C. Wallace

    (University of Pennsylvania)

  • Bruce M. Spiegelman

    (Harvard Medical School)

  • Yuriy Kirichok

    (University of California San Francisco)

Abstract

The mitochondrial ADP/ATP carrier (AAC) is a major transport protein of the inner mitochondrial membrane. It exchanges mitochondrial ATP for cytosolic ADP and controls cellular production of ATP. In addition, it has been proposed that AAC mediates mitochondrial uncoupling, but it has proven difficult to demonstrate this function or to elucidate its mechanisms. Here we record AAC currents directly from inner mitochondrial membranes from various mouse tissues and identify two distinct transport modes: ADP/ATP exchange and H+ transport. The AAC-mediated H+ current requires free fatty acids and resembles the H+ leak via the thermogenic uncoupling protein 1 found in brown fat. The ADP/ATP exchange via AAC negatively regulates the H+ leak, but does not completely inhibit it. This suggests that the H+ leak and mitochondrial uncoupling could be dynamically controlled by cellular ATP demand and the rate of ADP/ATP exchange. By mediating two distinct transport modes, ADP/ATP exchange and H+ leak, AAC connects coupled (ATP production) and uncoupled (thermogenesis) energy conversion in mitochondria.

Suggested Citation

  • Ambre M. Bertholet & Edward T. Chouchani & Lawrence Kazak & Alessia Angelin & Andriy Fedorenko & Jonathan Z. Long & Sara Vidoni & Ryan Garrity & Joonseok Cho & Naohiro Terada & Douglas C. Wallace & Br, 2019. "H+ transport is an integral function of the mitochondrial ADP/ATP carrier," Nature, Nature, vol. 571(7766), pages 515-520, July.
    • Handle: RePEc:nat:nature:v:571:y:2019:i:7766:d:10.1038_s41586-019-1400-3
    DOI: 10.1038/s41586-019-1400-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-019-1400-3
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-019-1400-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Antoine Gagelin & Corentin Largeau & Sandrine Masscheleyn & Mathilde S. Piel & Daniel Calderón-Mora & Frédéric Bouillaud & Jérôme Hénin & Bruno Miroux, 2023. "Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Xiaoting Sun & Wenhai Sui & Zepeng Mu & Sisi Xie & Jinxiu Deng & Sen Li & Takahiro Seki & Jieyu Wu & Xu Jing & Xingkang He & Yangang Wang & Xiaokun Li & Yunlong Yang & Ping Huang & Minghua Ge & Yihai , 2023. "Mirabegron displays anticancer effects by globally browning adipose tissues," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Chen, Shuxian & Dai, Xiaohu & Yang, Donghai & Dai, Lingling & Hua, Yu, 2023. "Enhancing PHA production through metal-organic frameworks: Mechanisms involving superproton transport and bacterial metabolic pathways," Applied Energy, Elsevier, vol. 348(C).
    4. Erminia Donnarumma & Michael Kohlhaas & Elodie Vimont & Etienne Kornobis & Thibault Chaze & Quentin Giai Gianetto & Mariette Matondo & Maryse Moya-Nilges & Christoph Maack & Timothy Wai, 2022. "Mitochondrial Fission Process 1 controls inner membrane integrity and protects against heart failure," Nature Communications, Nature, vol. 13(1), pages 1-24, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:571:y:2019:i:7766:d:10.1038_s41586-019-1400-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.