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嵴通过 MICOS 依赖性的连续膜重塑循环。

Cristae undergo continuous cycles of membrane remodelling in a MICOS-dependent manner.

机构信息

Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Faculty of Mathematics and Natural Sciences, Center for Advanced Imaging, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

出版信息

EMBO Rep. 2020 Mar 4;21(3):e49776. doi: 10.15252/embr.201949776. Epub 2020 Feb 18.

DOI:10.15252/embr.201949776
PMID:32067344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7054676/
Abstract

The mitochondrial inner membrane can reshape under different physiological conditions. How, at which frequency this occurs in living cells, and the molecular players involved are unknown. Here, we show using state-of-the-art live-cell stimulated emission depletion (STED) super-resolution nanoscopy that neighbouring crista junctions (CJs) dynamically appose and separate from each other in a reversible and balanced manner in human cells. Staining of cristae membranes (CM), using various protein markers or two lipophilic inner membrane-specific dyes, further revealed that cristae undergo continuous cycles of membrane remodelling. These events are accompanied by fluctuations of the membrane potential within distinct cristae over time. Both CJ and CM dynamics depended on MIC13 and occurred at similar timescales in the range of seconds. Our data further suggest that MIC60 acts as a docking platform promoting CJ and contact site formation. Overall, by employing advanced imaging techniques including fluorescence recovery after photobleaching (FRAP), single-particle tracking (SPT), live-cell STED and high-resolution Airyscan microscopy, we propose a model of CJ dynamics being mechanistically linked to CM remodelling representing cristae membrane fission and fusion events occurring within individual mitochondria.

摘要

线粒体的内膜可以在不同的生理条件下重塑。在活细胞中，这种重塑以何种频率发生，涉及哪些分子机制尚不清楚。在这里，我们利用最先进的活细胞受激发射损耗（STED）超分辨率纳米显微镜技术显示，在人类细胞中，相邻的嵴突连接（CJs）以可逆和平衡的方式动态靠拢和分离。使用各种蛋白标记物或两种亲脂性内膜特异性染料对嵴突膜（CM）进行染色，进一步表明嵴突经历了连续的膜重塑循环。这些事件伴随着跨时间嵴突内膜电位的波动。CJ 和 CM 的动力学都依赖于 MIC13，并且在几秒钟的相似时间尺度内发生。我们的数据进一步表明，MIC60 作为一个停泊平台促进了 CJ 和接触位点的形成。总的来说，通过采用先进的成像技术，包括光漂白后荧光恢复（FRAP）、单颗粒追踪（SPT）、活细胞 STED 和高分辨率 Airyscan 显微镜，我们提出了一个模型，表明 CJ 的动力学与 CM 的重塑有关，这代表了单个线粒体中嵴突膜裂变和融合事件的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7380/7054676/8be23cdcf0cf/EMBR-21-e49776-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7380/7054676/7bc466f976c2/EMBR-21-e49776-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7380/7054676/927c97cfec21/EMBR-21-e49776-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7380/7054676/29ccb45fbf44/EMBR-21-e49776-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7380/7054676/4ca5f508340d/EMBR-21-e49776-g013.jpg
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Live-cell STED nanoscopy of mitochondrial cristae.活细胞 STED 纳米超分辨显微镜观察线粒体嵴。
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