小柯机器人

科学家实现对肺癌线粒体膜电位的体内成像
2019-10-31 16:31

近日,美国加州大学洛杉矶分析David B. Shackelford课题组实现了对非小细胞肺癌线粒体膜电位的体内成像。这一研究成果于10月30日在线发表在《自然》上。

研究人员使用电压敏感的正电子发射断层扫描(PET)放射性示踪剂,称为18F-BnTP(4-[18F]fluorobenzyl-triphenylphosphonium),测量体内非小细胞肺癌的线粒体膜电位。通过使用18F-BnTP的PET成像,研究人员在肺癌原发小鼠模型中分析了线粒体膜的电位,并在肺肿瘤亚型中发现了不同的功能性线粒体异质性。18F-BnTP PET成像的使用使研究人员能够在功能上分析活体肿瘤中线粒体膜电位。

研究人员表示,线粒体是细胞能量和代谢的重要调节者,并且在维持癌细胞的生长和存活中起关键作用。线粒体的主要功能是通过氧化磷酸化合成ATP,这被称为线粒体生物能量学。线粒体通过产生由电子传输链产生的膜电位梯度来驱动ATP的合成,从而维持氧化磷酸化作用。线粒体对于在细胞培养和异种移植物中肿瘤的发生和维持肿瘤细胞的生长是必不可少的。但是,由于大多数研究是在细胞培养模型中进行的,因此我们对癌症中氧化性线粒体代谢的了解有限。这突出了需要进行体内研究以更好地理解氧化代谢如何支持肿瘤生长的需求。

附:英文原文

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

Author: Milica Momcilovic, Anthony Jones, Sean T. Bailey, Christopher M. Waldmann, Rui Li, Jason T. Lee, Gihad Abdelhady, Adrian Gomez, Travis Holloway, Ernst Schmid, David Stout, Michael C. Fishbein, Linsey Stiles, Deepa V. Dabir, Steven M. Dubinett, Heather Christofk, Orian Shirihai, Carla M. Koehler, Saman Sadeghi, David B. Shackelford

Issue&Volume: 2019-10-30

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. A positron emission tomography imaging tracer is developed to image mitochondrial function in vivo, and application of this tracer to a mouse model of lung cancer identifies distinct functional mitochondrial heterogeneity between tumour cells.

DOI: 10.1038/s41586-019-1715-0

Source:https://www.nature.com/articles/s41586-019-1715-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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