Subcellular connectomic analyses of energy networks in striated muscle.

Subcellular connectomic analyses of energy networks in striated muscle.
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横纹肌肉中能量网络的亚细胞连接分析。

DOI:
10.1038/s41467-018-07676-y
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发表时间:
2018-11-30
影响因子:
16.6
通讯作者:
Glancy B
Glancy B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bleck CKE;Kim Y;Willingham TB;Glancy B

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绘制生物电路连接图彻底改变了我们对结构-功能关系的理解。虽然connectomic分析主要集中在神经系统,肌肉线粒体网络内的电连接最近被证明提供了一个快速的机制,细胞能量分布。然而,目前缺乏在单细胞内以高空间保真度评估细胞器连接的工具。在这里,我们开发了一个框架,以定量评估线粒体网络的连接和相互作用的能量储存,利用和钙循环在心脏,氧化和糖酵解肌肉的细胞位点。我们证明,线粒体网络配置,单个线粒体的大小和形状,以及连接每个网络内的线粒体的连接点与每种肌肉类型的不同收缩需求是一致的。此外,线粒体-脂滴相互作用分析表明,网络内的单个线粒体可能在细胞内的能量分布和钙循环方面发挥专门的作用,并揭示了单细胞内细胞器相互作用的连接组学分析的力量。由于缺乏适当的工具,评估单细胞中的生物回路连接一直很棘手。在这里,Bleck等人开发了一种方法来评估肌肉细胞中的线粒体网络连接,并观察到与不同能量需求一致的明显差异。
Mapping biological circuit connectivity has revolutionized our understanding of structure-function relationships. Although connectomic analyses have primarily focused on neural systems, electrical connectivity within muscle mitochondrial networks was recently demonstrated to provide a rapid mechanism for cellular energy distribution. However, tools to evaluate organelle connectivity with high spatial fidelity within single cells are currently lacking. Here, we developed a framework to quantitatively assess mitochondrial network connectivity and interactions with cellular sites of energy storage, utilization, and calcium cycling in cardiac, oxidative, and glycolytic muscle. We demonstrate that mitochondrial network configuration, individual mitochondrial size and shape, and the junctions connecting mitochondria within each network are consistent with the differing contraction demands of each muscle type. Moreover, mitochondria-lipid droplet interaction analyses suggest that individual mitochondria within networks may play specialized roles regarding energy distribution and calcium cycling within the cell and reveal the power of connectomic analyses of organelle interactions within single cells. Assessing biological circuit connections in single cells has been intractable due to lack of appropriate tools. Here, Bleck et al. develop a method to assess mitochondrial network connectivity in muscle cells and observe clear differences consistent with differing energy requirements.
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