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Nature. 2019 Nov;575(7782):380-384. doi: 10.1038/s41586-019-1715-0. Epub 2019 Oct 30.

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

Author information

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.
2
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
3
The Mouse Phase I Unit, Lineberger School of Medicine at the University of North Carolina Chapel Hill, Chapel Hill, NC, USA.
4
Crump Institute for Molecular Imaging, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
5
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
6
Department of Chemistry and Biochemistry, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
7
Department of Biological Chemistry, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
8
Regis College, Weston, MA, USA.
9
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
10
Department of Endocrinology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
11
Department of Biology, Loyola Marymount University, Los Angeles, CA, USA.
12
VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
13
UCLA Metabolomics Center, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
14
Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. dshackelford@mednet.ucla.edu.
15
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. dshackelford@mednet.ucla.edu.

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.

PMID:
31666695
DOI:
10.1038/s41586-019-1715-0

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