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In vivo quantification of mitochondrial membrane potential

Nature volume 583, pages E17–E18 (2020)Cite this article

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Matters Arising to this article was published on 08 July 2020

The Original Article was published on 30 October 2019

arising from: M. Momcilovic et al. Nature https://doi.org/10.1038/s41586-019-1715-0 (2019)

The recent paper by Momcilovic et al.1 presents important results on mitochondrial metabolism differences among various lung cancer subtypes in mouse. However, the work1 propagates critical misunderstandings and omissions about the underlying basis for the application of voltage-sensing tracers. The principle of imaging of mitochondrial membrane potential (ΔΨm) with radiolabelled positron emission tomography (PET) probes is based on benchtop in vitro methods. In vitro quantification of ΔΨm has been established for decades using various lipophilic cations such as 3H-tetraphenylphosphonium (3H-TPP+)2,3,4. In all cases, the Nernst equation is used to relate the equilibrium concentration of the probe on either side of a membrane to the electric potential across the membrane5. Importantly, the Nernst equation is only valid when probe concentrations are at equilibrium—that is, the concentrations on either side of the membrane are not changing with time.

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References

  1. 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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Acknowledgements

The authors gratefully acknowledge support from NIH grants P41-EB022544 and R01-HL137230. These grants were awarded as part of the standard peer review process for new grants. The study design and analysis are solely the work of the study authors and the funders had no role in the study.

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Authors and Affiliations

  1. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Nathaniel M. Alpert, Matthieu Pelletier-Galarneau, Yoann Petibon, Marc D. Normandin & Georges El Fakhri

  2. Department of Medical Imaging, Montreal Heart Institute, Montreal, Quebec, Canada

    Matthieu Pelletier-Galarneau

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  1. Nathaniel M. Alpert
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  2. Matthieu Pelletier-Galarneau
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  4. Marc D. Normandin
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  5. Georges El Fakhri
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Contributions

N.M.A. contributed the overall measurement strategy. M.P.-G. wrote the first draft. Y.P., M.D.N. and G.E.F. edited and revised the manuscript.

Corresponding author

Correspondence to Nathaniel M. Alpert.

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Competing interests

The authors are employed by The General Hospital Corporation, Partners Healthcare, Boston, MA, USA. US patent US20190125281A1, ‘System and method for quantitatively mapping mitochondrial membrane potential’ (status pending) is assigned to The General Hospital Corporation and lists N.M.A., G.E.F., M.D.N. and N. Guehl as inventors.

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Alpert, N.M., Pelletier-Galarneau, M., Petibon, Y. et al. In vivo quantification of mitochondrial membrane potential. Nature 583, E17–E18 (2020). https://doi.org/10.1038/s41586-020-2366-x

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