In-cell structures of conserved supramolecular protein arrays at the mitochondria-cytoskeleton interface in mammalian sperm.
In-cell structures of conserved supramolecular protein arrays at the mitochondria-cytoskeleton interface in mammalian sperm.
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DOI：
10.1073/pnas.2110996118
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发表时间：
2021-11-09
影响因子：
11.1
通讯作者：
Zeev-Ben-Mordehai T
中科院分区：
文献类型：
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作者：
Leung MR;Zenezini Chiozzi R;Roelofs MC;Hevler JF;Ravi RT;Maitan P;Zhang M;Henning H;Bromfield EG;Howes SC;Gadella BM;Heck AJR;Zeev-Ben-Mordehai T
线粒体的空间组织对于细胞功能至关重要。在许多专门的细胞类型中，线粒体通过与细胞骨架的相互作用固定在特定的亚细胞位点。最引人注目的线粒体构型之一出现在哺乳动物精子中，线粒体包裹在鞭毛周围。线粒体鞘的畸形会导致不孕，但这种复杂排列背后的分子结构尚不清楚。在这里，我们分析了三种哺乳动物精子中的线粒体鞘。我们发现，尽管线粒体尺寸和嵴结构因物种而异，但介导线粒体间和线粒体-细胞骨架相互作用的分子组装是保守的。这些发现为精子生理学和进化提供了重要的见解，并且与其他极化细胞类型相关，例如肌肉、神经元、光感受器和毛细胞。线粒体-细胞骨架相互作用通过调节线粒体运输、定位和固定来调节细胞生理学。然而，在任何细胞类型中，定义线粒体-细胞骨架界面的结构信息都非常少。在这里，我们使用冷冻聚焦离子束铣削冷冻电子断层扫描对哺乳动物精子进行成像，其中线粒体包裹着鞭毛细胞骨架。我们发现线粒体通过线粒体间连接体与其邻居相连，并通过线粒体外膜上的有序阵列锚定到细胞骨架上。我们使用次断层图平均来解析来自三种哺乳动物物种的这些阵列的细胞内结构，揭示尽管线粒体尺寸和嵴组织存在差异，但它们在物种间是保守的。我们发现该阵列由锚定在膜孔网络上的船形颗粒组成，其排列和尺寸与电压依赖性阴离子通道一致。蛋白质组学和细胞内交联质谱表明保守阵列由甘油激酶样蛋白组成。有序的超分子组装体可用于稳定其他细胞类型中的类似接触位点，其中线粒体需要固定在特定的亚细胞环境中，例如肌肉和神经元中。
Spatial organization of mitochondria is vital for cellular function. In many specialized cell types, mitochondria are immobilized at specific subcellular loci through interactions with the cytoskeleton. One of the most striking mitochondrial configurations occurs in mammalian sperm, where mitochondria wrap around the flagellum. Malformation of the mitochondrial sheath causes infertility, but the molecular structures underlying this intricate arrangement are unknown. Here, we analyzed the mitochondrial sheath in sperm from three mammalian species. We find that although mitochondrial dimensions and cristae architecture vary across species, molecular assemblies mediating intermitochondria and mitochondria–cytoskeleton interactions are conserved. These findings yield important insight into sperm physiology and evolution and are relevant for other polarized cell types, such as muscles, neurons, photoreceptors, and hair cells. Mitochondria–cytoskeleton interactions modulate cellular physiology by regulating mitochondrial transport, positioning, and immobilization. However, there is very little structural information defining mitochondria–cytoskeleton interfaces in any cell type. Here, we use cryofocused ion beam milling-enabled cryoelectron tomography to image mammalian sperm, where mitochondria wrap around the flagellar cytoskeleton. We find that mitochondria are tethered to their neighbors through intermitochondrial linkers and are anchored to the cytoskeleton through ordered arrays on the outer mitochondrial membrane. We use subtomogram averaging to resolve in-cell structures of these arrays from three mammalian species, revealing they are conserved across species despite variations in mitochondrial dimensions and cristae organization. We find that the arrays consist of boat-shaped particles anchored on a network of membrane pores whose arrangement and dimensions are consistent with voltage-dependent anion channels. Proteomics and in-cell cross-linking mass spectrometry suggest that the conserved arrays are composed of glycerol kinase-like proteins. Ordered supramolecular assemblies may serve to stabilize similar contact sites in other cell types in which mitochondria need to be immobilized in specific subcellular environments, such as in muscles and neurons.
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甘油激酶样蛋白与 Pld6 协同调节精子线粒体鞘形成和男性生育力
影响因子：
33.5
作者：
Chen Y;Liang P;Huang Y;Li M;Zhang X;Ding C;Feng J;Zhang Z;Zhang X;Gao Y;Zhang Q;Cao S;Zheng H;Liu D;Songyang Z;Huang J
通讯作者：
Huang J
影响因子：
2.5
作者：
HARRISON, RAP;MAIRET, B;MILLER, NGA
通讯作者：
MILLER, NGA
DOI：
10.1095/biolreprod2.supplement_2.90
发表时间：
1970-01-01
期刊：
Biol. Reprod.
影响因子：
--
作者：
Fawcett, D. W.
通讯作者：
Fawcett, D. W.
影响因子：
3.6
作者：
Balbach, Melanie;Gervasi, Maria Gracia;Buck, Jochen
通讯作者：
Buck, Jochen
影响因子：
16.6
作者：
通讯作者：
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