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

被引：167

作者：

Momcilovic, Milica ^{[1
]}

Jones, Anthony ^{[2
]}

Bailey, Sean T. ^{[3
]}

Waldmann, Christopher M. ^{[2
]}

Li, Rui ^{[1
]}

Lee, Jason T. ^{[3
,4
,5
]}

Abdelhady, Gihad ^{[1
]}

Gomez, Adrian ^{[6
]}

Holloway, Travis ^{[2
]}

Schmid, Ernst ^{[7
]}

Stout, David ^{[8
]}

Fishbein, Michael C. ^{[9
]}

Stiles, Linsey ^{[10
]}

Dabir, Deepa V. ^{[11
]}

Dubinett, Steven M. ^{[1
,2
,5
,9
,12
]}

Christofk, Heather ^{[2
,5
,7
,13
]}

Shirihai, Orian ^{[5
,10
]}

Koehler, Carla M. ^{[6
]}

Sadeghi, Saman ^{[2
]}

Shackelford, David B. ^{[1
,5
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[3] Univ N Carolina, Lineberger Sch Med, Mouse Phase Unit 1, Chapel Hill, NC 27515 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

[8] Regis Coll, Weston, MA USA

[9] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[10] Univ Calif Los Angeles, David Geffen Sch Med, Dept Endocrinol, Los Angeles, CA 90095 USA

[11] Loyola Marymount Univ, Dept Biol, Los Angeles, CA 90045 USA

[12] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA

[13] Univ Calif Los Angeles, David Geffen Sch Med, Metab Ctr, Los Angeles, CA 90095 USA

来源：

NATURE | 2019年 / 575卷 / 7782期

关键词：

VOLTAGE SENSOR; METABOLISM; METFORMIN; ROTENONE;

D O I：

10.1038/s41586-019-1715-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 ATP(1). Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts(2,3). 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-[F-18]fluorobenzyl-triphenylphosphonium (F-18-BnTP)(4). By using PET imaging of F-18-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 F-18-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.

引用

页码：380 / +

页数：18

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