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In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer

Author

Listed:
  • Milica Momcilovic

    (David Geffen School of Medicine at the University of California)

  • Anthony Jones

    (David Geffen School of Medicine at the University of California)

  • Sean T. Bailey

    (The Mouse Phase I Unit, Lineberger School of Medicine at the University of North Carolina Chapel Hill)

  • Christopher M. Waldmann

    (David Geffen School of Medicine at the University of California)

  • Rui Li

    (David Geffen School of Medicine at the University of California)

  • Jason T. Lee

    (David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California)

  • Gihad Abdelhady

    (David Geffen School of Medicine at the University of California)

  • Adrian Gomez

    (David Geffen School of Medicine at the University of California)

  • Travis Holloway

    (David Geffen School of Medicine at the University of California)

  • Ernst Schmid

    (David Geffen School of Medicine at the University of California)

  • David Stout

    (Regis College)

  • Michael C. Fishbein

    (David Geffen School of Medicine at the University of California)

  • Linsey Stiles

    (David Geffen School of Medicine at the University of California)

  • Deepa V. Dabir

    (Loyola Marymount University)

  • Steven M. Dubinett

    (David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California)

  • Heather Christofk

    (David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California)

  • Orian Shirihai

    (David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California)

  • Carla M. Koehler

    (David Geffen School of Medicine at the University of California)

  • Saman Sadeghi

    (David Geffen School of Medicine at the University of California)

  • David B. Shackelford

    (David Geffen School of Medicine at the University of California
    David Geffen School of Medicine at the University of California)

Abstract

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.

Suggested Citation

  • Milica Momcilovic & Anthony Jones & Sean T. Bailey & Christopher M. Waldmann & Rui Li & Jason T. Lee & Gihad Abdelhady & Adrian Gomez & Travis Holloway & Ernst Schmid & David Stout & Michael C. Fishbe, 2019. "In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer," Nature, Nature, vol. 575(7782), pages 380-384, November.
    • Handle: RePEc:nat:nature:v:575:y:2019:i:7782:d:10.1038_s41586-019-1715-0
    DOI: 10.1038/s41586-019-1715-0
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    Citations

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    Cited by:

    1. Yanan Li & Yonghua Wu & Ru Xu & Jialing Guo & Fenglei Quan & Yongyuan Zhang & Di Huang & Yiran Pei & Hua Gao & Wei Liu & Junjie Liu & Zhenzhong Zhang & Ruijie Deng & Jinjin Shi & Kaixiang Zhang, 2023. "In vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Shan Lei & Jing Zhang & Nicholas Thomas Blum & Meng Li & Dong-Yang Zhang & Weimin Yin & Feng Zhao & Jing Lin & Peng Huang, 2022. "In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Haiwang Yang & Qianru Li & Emily K. Stroup & Sheng Wang & Zhe Ji, 2024. "Widespread stable noncanonical peptides identified by integrated analyses of ribosome profiling and ORF features," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Christopher W. Murray & Jennifer J. Brady & Mingqi Han & Hongchen Cai & Min K. Tsai & Sarah E. Pierce & Ran Cheng & Janos Demeter & David M. Feldser & Peter K. Jackson & David B. Shackelford & Monte M, 2022. "LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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