TY - JOUR
T1 - In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer
AU - Momcilovic, Milica
AU - Jones, Anthony
AU - Bailey, Sean T.
AU - Waldmann, Christopher M.
AU - Li, Rui
AU - Lee, Jason T.
AU - Abdelhady, Gihad
AU - Gomez, Adrian
AU - Holloway, Travis
AU - Schmid, Ernst
AU - Stout, David
AU - Fishbein, Michael C.
AU - Stiles, Linsey
AU - Dabir, Deepa V.
AU - Dubinett, Steven M.
AU - Christofk, Heather
AU - Shirihai, Orian
AU - Koehler, Carla M.
AU - Sadeghi, Saman
AU - Shackelford, David B.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/11/14
Y1 - 2019/11/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074696871&partnerID=8YFLogxK
U2 - 10.1038/s41586-019-1715-0
DO - 10.1038/s41586-019-1715-0
M3 - Article
C2 - 31666695
AN - SCOPUS:85074696871
SN - 0028-0836
VL - 575
SP - 380
EP - 384
JO - Nature
JF - Nature
IS - 7782
ER -
