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Access through your institution Buy or subscribe 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 (Δ_Ψ_m) with radiolabelled positron emission tomography (PET)

probes is based on benchtop in vitro methods. In vitro quantification of Δ_Ψ_m 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. This is a

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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Momcilovic, M. et al. In vivo imaging of mitochondrial membrane potential in

non-small-cell lung cancer. _Nature_ 575, 380–384 (2019). Article  CAS  ADS  Google Scholar  * Kauppinen, R. Proton electrochemical potential of the inner mitochondrial membrane in isolated

perfused rat hearts, as measured by exogenous probes. _Biochim. Biophys. Acta_ 725, 131–137 (1983). Article  CAS  Google Scholar  * Rottenberg, H. Membrane potential and surface potential in

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Jonen. _Z. Phys. Chem_. 4, 129–181 (1889). Google Scholar  * Alpert, N. M. et al. Quantitative in vivo mapping of myocardial mitochondrial membrane potential. _PLoS One_ 13, e0190968 (2018);

correction 13, e0192876 (2018). Article  Google Scholar  Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * Department of Medical Imaging, Montreal Heart Institute, Montreal, Quebec,

Canada Matthieu Pelletier-Galarneau Authors * Nathaniel M. Alpert View author publications You can also search for this author inPubMed Google Scholar * Matthieu Pelletier-Galarneau View

author publications You can also search for this author inPubMed Google Scholar * Yoann Petibon View author publications You can also search for this author inPubMed Google Scholar * Marc D.

Normandin View author publications You can also search for this author inPubMed Google Scholar * Georges El Fakhri View author publications You can also search for this author inPubMed 

Google Scholar 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. ETHICS DECLARATIONS 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. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional

affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 27 November 2019 * Accepted: 20 April 2020 *

Published: 08 July 2020 * Issue Date: 09 July 2020 * DOI: https://doi.org/10.1038/s41586-020-2366-x SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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