In Vivo Quantification of Mitochondrial Membrane Potential

Abstract

Momcilovic et al1 report mitochondrial metabolism differences amongst various mouse lung cancer subtypes, as measured by positron emission tomography (PET) and a voltage-sensitive tracer. They describe their experiments as measurements of mitochondrial membrane potential, ΔΨm, and suggest that they might be used as a non-invasive biomarker to guide the delivery of complex I inhibitors in cancer. Contrary to their claims, Momcilovic et al did not measure membrane potential in an absolute sense, instead relying on an empirical endpoint, namely the percent dose per gram of the tracer in tumor to that in heart, which only partially depends on ΔΨm. Despite the biomedical significance of their findings, their work represents critical methodological misunderstandings and omissions about the underlying basis for application of voltage sensing tracers which could ultimately hinder the successful clinical translation of the technique.