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细胞凋亡诱导核膜 nesprin-2 向线粒体易位与线粒体功能障碍有关。

Apoptosis-induced translocation of nesprin-2 from the nuclear envelope to mitochondria is associated with mitochondrial dysfunction.

机构信息

School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

出版信息

Nucleus. 2024 Dec;15(1):2413501. doi: 10.1080/19491034.2024.2413501. Epub 2024 Oct 15.

DOI:10.1080/19491034.2024.2413501
PMID:39402980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11486236/
Abstract

Accumulating evidence suggests that the nuclear envelope (NE) is not just a target, but also a mediator of apoptosis. We showed recently that the NE protein nesprin-2 has pro-apoptotic activity, which involves its subcellular redistribution and Bcl-2 proteins. Here we further characterize the pro-apoptotic activity of nesprin-2 focusing on its redistribution. We assessed the redistribution kinetics of endogenous nesprin-2 tagged with GFP relative to apoptosis-associated mitochondrial dysfunction. The results show apoptosis-induced GFP-nesprin-2G redistribution occurred by two different modes - complete and partial, both lead to appearance of nesprin-2G near the mitochondria. Moreover, GFP-nesprin-2 redistribution is associated with reduction in mitochondrial membrane potential and mitochondrial outer membrane permeabilization and precedes the appearance of morphological features of apoptosis. Our results show that nesprin-2G redistribution and translocation near mitochondria is an early apoptotic effect associated with mitochondrial dysfunction, which may be responsible for the pro-apoptotic function of nesprin-2.

摘要

越来越多的证据表明，核膜（NE）不仅是凋亡的靶点，也是凋亡的介质。我们最近发现，核膜蛋白 nesprin-2 具有促凋亡活性，涉及它的亚细胞重新分布和 Bcl-2 蛋白。在这里，我们进一步研究了 nesprin-2 的促凋亡活性，重点研究其重新分布。我们评估了与凋亡相关的线粒体功能障碍相关的内源性 GFP 标记 nesprin-2 的重分布动力学。结果表明，凋亡诱导的 GFP-nesprin-2G 完全和部分重新分布都会导致 nesprin-2G 出现在线粒体附近。此外，GFP-nesprin-2 的重新分布与线粒体膜电位降低和线粒体外膜通透性增加有关，并且早于凋亡形态特征的出现。我们的结果表明，nesprin-2G 在向线粒体附近的重新分布和易位是与线粒体功能障碍相关的早期凋亡效应，这可能是 nesprin-2 促凋亡功能的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/5beb53b1a959/KNCL_A_2413501_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/980de55b79f7/KNCL_A_2413501_F0005b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/b56bef635e06/KNCL_A_2413501_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/db2c11fad454/KNCL_A_2413501_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/22454c1584df/KNCL_A_2413501_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/69f3c3bd6349/KNCL_A_2413501_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/4f30eabc83c3/KNCL_A_2413501_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/9640b65c075d/KNCL_A_2413501_F0005a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/5beb53b1a959/KNCL_A_2413501_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/980de55b79f7/KNCL_A_2413501_F0005b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/b56bef635e06/KNCL_A_2413501_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/db2c11fad454/KNCL_A_2413501_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/22454c1584df/KNCL_A_2413501_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/69f3c3bd6349/KNCL_A_2413501_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/4f30eabc83c3/KNCL_A_2413501_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/9640b65c075d/KNCL_A_2413501_F0005a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7011/11486236/5beb53b1a959/KNCL_A_2413501_F0007_OC.jpg

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Cell Death Discov. 2024 Jan 15;10(1):29. doi: 10.1038/s41420-023-01763-w.
2
Expanding roles of BCL-2 proteins in apoptosis execution and beyond.BCL-2 蛋白在细胞凋亡执行及其他方面的作用不断扩大。
J Cell Sci. 2023 Nov 15;136(22). doi: 10.1242/jcs.260790. Epub 2023 Nov 23.
3
Building and breaking mechanical bridges between the nucleus and cytoskeleton: Regulation of LINC complex assembly and disassembly.
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Curr Opin Cell Biol. 2023 Dec;85:102260. doi: 10.1016/j.ceb.2023.102260. Epub 2023 Oct 17.
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Mechanisms of BCL-2 family proteins in mitochondrial apoptosis.BCL-2 家族蛋白在线粒体凋亡中的作用机制。
Nat Rev Mol Cell Biol. 2023 Oct;24(10):732-748. doi: 10.1038/s41580-023-00629-4. Epub 2023 Jul 12.
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