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研究绘制肺癌线粒体网络和生物能量学的空间图谱
2023-03-23 11:41

美国加州大学洛杉矶分校David B. Shackelford团队近期取得重要工作进展,他们研究绘制了肺癌线粒体网络和生物能量学的空间图谱。相关研究成果2023年3月15日在线发表于《自然》杂志上。

据介绍,线粒体对于控制癌细胞的新陈代谢和生物能量学至关重要。 线粒体形成高度组织化的网络,其中它们的外膜和内膜结构决定了它们的生物能量容量。 然而,描绘线粒体网络的结构组织与其生物能量活性之间关系的体内研究受到限制。

研究人员使用由正电子发射断层扫描成像、呼吸测量和三维扫描块面电子显微镜组成的集成平台,对非小细胞肺癌 (NSCLC) 中的线粒体网络和生物能量表型进行了体内结构和功能分析。研究人员在NSCLC肿瘤中发现的多种生物能量表型和代谢依赖性与存在的线粒体网络不同结构组织一致。

此外,研究人员发现线粒体网络被组织成肿瘤细胞内不同的隔室。在具有高氧化磷酸化率 (OXPHOSHI) 和脂肪酸氧化率的肿瘤中,研究人员发现了液滴周围的线粒体网络,其中线粒体接触并包围脂滴。相比之下,研究人员发现在 OXPHOS (OXPHOSLO) 发生率低的肿瘤中,高葡萄糖通量调节线粒体的核周定位、嵴结构重塑和线粒体的呼吸能力。

总之,这一发现表明,在NSCLC中,线粒体网络被划分为不同的亚群,这些亚群控制着肿瘤的生物能量能力。

附:英文原文

Title: Spatial mapping of mitochondrial networks and bioenergetics in lung cancer

Author: Han, Mingqi, Bushong, Eric A., Segawa, Mayuko, Tiard, Alexandre, Wong, Alex, Brady, Morgan R., Momcilovic, Milica, Wolf, Dane M., Zhang, Ralph, Petcherski, Anton, Madany, Matthew, Xu, Shili, Lee, Jason T., Poyurovsky, Masha V., Olszewski, Kellen, Holloway, Travis, Gomez, Adrian, John, Maie St., Dubinett, Steven M., Koehler, Carla M., Shirihai, Orian S., Stiles, Linsey, Lisberg, Aaron, Soatto, Stefano, Sadeghi, Saman, Ellisman, Mark H., Shackelford, David B.

Issue&Volume: 2023-03-15

Abstract: Mitochondria are critical to the governance of metabolism and bioenergetics in cancer cells1. The mitochondria form highly organized networks, in which their outer and inner membrane structures define their bioenergetic capacity2,3. However, in vivo studies delineating the relationship between the structural organization of mitochondrial networks and their bioenergetic activity have been limited. Here we present an in vivo structural and functional analysis of mitochondrial networks and bioenergetic phenotypes in non-small cell lung cancer (NSCLC) using an integrated platform consisting of positron emission tomography imaging, respirometry and three-dimensional scanning block-face electron microscopy. The diverse bioenergetic phenotypes and metabolic dependencies we identified in NSCLC tumours align with distinct structural organization of mitochondrial networks present. Further, we discovered that mitochondrial networks are organized into distinct compartments within tumour cells. In tumours with high rates of oxidative phosphorylation (OXPHOSHI) and fatty acid oxidation, we identified peri-droplet mitochondrial networks wherein mitochondria contact and surround lipid droplets. By contrast, we discovered that in tumours with low rates of OXPHOS (OXPHOSLO), high glucose flux regulated perinuclear localization of mitochondria, structural remodelling of cristae and mitochondrial respiratory capacity. Our findings suggest that in NSCLC, mitochondrial networks are compartmentalized into distinct subpopulations that govern the bioenergetic capacity of tumours.

DOI: 10.1038/s41586-023-05793-3

Source: https://www.nature.com/articles/s41586-023-05793-3

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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