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Reply to: In vivo quantification of mitochondrial membrane potential

Nature volume 583, pages E19–E20 (2020)Cite this article

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The Original Article was published on 08 July 2020

replying to: N. M. Alpert et al. Nature https://doi.org/10.1038/s41586-020-2366-x (2020)

We thank the authors of the accompanying Comment1 for their interest in our work and acknowledging the biomedical significance of our recent multi-disciplinary study using positron emission tomography (PET) imaging to assess mitochondrial membrane potential in vivo within lung tumours2. To accomplish this work we used the 18F-labelled lipophilic cation tracer 18F-BnTP as a tool to image lung tumours in mouse models and identified conserved differences in mitochondrial function within lung tumour subtypes. Our work, along with studies by others in the field3,4, builds upon prior work by Alpert and colleagues5 and demonstrates that 18F-BnTP accumulation within tissues is responsive to the voltage across the mitochondrial inner membrane, enabling measurement of relative changes in mitochondrial membrane potential in tissues such as the heart. However, although we acknowledge the work performed by Alpert et al. on measuring mitochondrial membrane potential, we disagree with their claims that our study “represents critical misunderstandings and omissions”1 regarding the underlying basis of the application of voltage-sensing tracers.

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References

  1. Alpert, N. M., Pelletier-Galarneau, M., Petibon, Y., Normandin, M. D. & El Fakhri, G. In vivo quantification of mitochondrial membrane potential. Nature https://doi.org/10.1038/s41586-020-2366-x (2020).

  2. Momcilovic, M. et al. In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer. Nature 575, 380–384 (2019).

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  3. Madar, I. et al. Characterization of membrane potential-dependent uptake of the novel PET tracer 18F-fluorobenzyl triphenylphosphonium cation. Eur. J. Nucl. Med. Mol. Imaging 34, 2057–2065 (2007).

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  4. Madar, I. et al. Characterization of uptake of the new PET imaging compound 18F-fluorobenzyl triphenyl phosphonium in dog myocardium. J. Nucl. Med. 47, 1359–1366 (2006).

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  5. Alpert, N. M. et al. Quantitative in vivo mapping of myocardial mitochondrial membrane potential. PLoS One 13, e0190968 (2018).

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

D.B.S. was supported by UCLA Jonsson Comprehensive Cancer Center grant P30 CA016042, Department of Defense LCRP grant W81XWH-13-1-0459 and NIH/NCI R01 CA208642-01. M.M. was supported by American Cancer Society Research Scholar grant RSG-16-234-01-TBG.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Milica Momcilovic & David B. Shackelford

  2. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Saman Sadeghi

  3. Department of Chemistry and Biochemistry, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Carla M. Koehler

  4. Department of Endocrinology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Orian Shirihai

  5. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA

    Orian Shirihai, Carla M. Koehler & David B. Shackelford

  6. MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK

    Michael P. Murphy

  7. Department of Medicine, University of Cambridge, Cambridge, UK

    Michael P. Murphy

Authors
  1. Milica Momcilovic
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  2. Orian Shirihai
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  3. Michael P. Murphy
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  4. Carla M. Koehler
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  5. Saman Sadeghi
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  6. David B. Shackelford
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Contributions

This Reply was submitted by D.B.S. and senior authors of the original Article, as well as M.P.M., all of whom have expertise directly related to the topic discussed in the accompanying Comment. D.B.S. wrote this Reply with expertise and critical feedback contributed by M.M., S.S., O.S., C.M.K. and M.P.M.

Corresponding author

Correspondence to David B. Shackelford.

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Competing interests

D.B.S., M.M. and S.S. have filed a provisional patent for the use of 18F-BnTP to guide the use of complex I inhibitors in the treatment of lung cancer.

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Momcilovic, M., Shirihai, O., Murphy, M. et al. Reply to: In vivo quantification of mitochondrial membrane potential. Nature 583, E19–E20 (2020). https://doi.org/10.1038/s41586-020-2367-9

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