Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network.
Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network.
复制标题
人类骨骼肌线粒体网络的定量 3D 绘图。
DOI：
10.1016/j.celrep.2019.03.051
复制
发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Picard,Martin
中科院分区：
文献类型：
--
作者：
Vincent,AmyE;White,Kathryn;Davey,Tracey;Philips,Jonathan;Ogden,RTodd;Lawless,Conor;Warren,Charlotte;Hall,MattG;Ng,YiShiau;Falkous,Gavin;Holden,Thomas;Deehan,David;Taylor,RobertW;Turnbull,DougM;Picard,Martin
线粒体功能的遗传和生化缺陷是人类疾病的主要原因，但它们与原位线粒体形态的联系尚未确定。在这里，我们开发了一种定量三维方法，以电子显微镜分辨率绘制人体肌肉中的线粒体网络组织。我们建立了人类和小鼠之间以及线粒体 DNA (mtDNA) 疾病患者与健康对照之间的形态差异。我们还定义了线粒体纳米隧道的超微结构和普遍性，线粒体纳米隧道以游离端或跨非相邻线粒体的连接膜突起的形式存在。整合线粒体体积、形态复杂性和跨个体线粒体和线粒体群体计算的分支各向异性的多变量模型将简单线粒体和纳米隧道的比例增加确定为线粒体应激的判别特征。总体而言，这些数据定义了人体肌肉中线粒体网络的性质，量化了人与小鼠的差异，并提出了人体组织中线粒体功能障碍的潜在形态学标记。
Genetic and biochemical defects of mitochondrial function are a major cause of human disease, but their link to mitochondrial morphologyin situhas not been defined. Here, we develop a quantitative three-dimensional approach to map mitochondrial network organization in human muscle at electron microscopy resolution. We establish morphological differences between human and mouse and among patients with mitochondrial DNA (mtDNA) diseases compared to healthy controls. We also define the ultrastructure and prevalence of mitochondrial nanotunnels, which exist as either free-ended or connecting membrane protrusions across non-adjacent mitochondria. A multivariate model integrating mitochondrial volume, morphological complexity, and branching anisotropy computed across individual mitochondria and mitochondrial populations identifies increased proportion of simple mitochondria and nanotunnels as a discriminant signature of mitochondrial stress. Overall, these data define the nature of the mitochondrial network in human muscle, quantify human-mouse differences, and suggest potential morphological markers of mitochondrial dysfunction in human tissues.