线粒体-溶酶体膜接触位点在细胞稳态中的调节和功能。
Regulation and Function of Mitochondria-Lysosome Membrane Contact Sites in Cellular Homeostasis.
机构信息
Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
出版信息
Trends Cell Biol. 2019 Jun;29(6):500-513. doi: 10.1016/j.tcb.2019.02.004. Epub 2019 Mar 18.
Abstract
Mitochondrial and lysosomal function are intricately related and critical for maintaining cellular homeostasis, as highlighted by multiple diseases linked to dysfunction of both organelles. Recent work using high-resolution microscopy demonstrates the dynamic formation of inter-organelle membrane contact sites between mitochondria and lysosomes, allowing for their direct interaction in a pathway distinct from mitophagy or lysosomal degradation of mitochondrial-derived vesicles. Mitochondria-lysosome contact site tethering is mechanistically regulated by mitochondrial proteins promoting Rab7 GTP hydrolysis, and allows for the bidirectional crosstalk between mitochondria and lysosomes and the regulation of their organelle network dynamics, including mitochondrial fission. In this review, we summarize recent advances in mitochondria-lysosome contact site regulation and function, and discuss their potential roles in cellular homeostasis and various human diseases.
摘要
线粒体和溶酶体的功能密切相关，对于维持细胞内稳态至关重要，这一点在与这两个细胞器功能障碍相关的多种疾病中得到了强调。最近使用高分辨率显微镜的研究表明，线粒体和溶酶体之间会形成细胞器间膜接触位点，从而允许它们在不同于自噬或溶酶体降解线粒体衍生小泡的途径中进行直接相互作用。线粒体-溶酶体接触点的连接通过促进 Rab7 GTP 水解的线粒体蛋白在机制上受到调节，并允许线粒体和溶酶体之间进行双向串扰，以及调节它们的细胞器网络动态，包括线粒体裂变。在这篇综述中，我们总结了线粒体-溶酶体接触点调节和功能的最新进展，并讨论了它们在细胞内稳态和各种人类疾病中的潜在作用。
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本文引用的文献
1
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Dis Model Mech. 2019 Feb 22;12(2):dmm036681. doi: 10.1242/dmm.036681.
2
Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.晚期内体充当 mRNA 翻译平台并维持轴突中的线粒体。
Cell. 2019 Jan 10;176(1-2):56-72.e15. doi: 10.1016/j.cell.2018.11.030. Epub 2019 Jan 3.
3
Visualizing Intracellular Organelle and Cytoskeletal Interactions at Nanoscale Resolution on Millisecond Timescales.在毫秒时间尺度上以纳米分辨率可视化细胞内细胞器和细胞骨架相互作用。
Cell. 2018 Nov 15;175(5):1430-1442.e17. doi: 10.1016/j.cell.2018.09.057. Epub 2018 Oct 25.
4
Super-Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore.基于铱（III）配合物的线粒体动力学超分辨追踪。
Small. 2018 Oct;14(41):e1802166. doi: 10.1002/smll.201802166. Epub 2018 Sep 14.
5
A novel lysosome-to-mitochondria signaling pathway disrupted by amyloid-β oligomers.淀粉样β寡聚体破坏的新型溶酶体到线粒体信号通路。
EMBO J. 2018 Nov 15;37(22). doi: 10.15252/embj.2018100241. Epub 2018 Oct 22.
6
Lysosomal storage diseases.溶酶体贮积症。
Nat Rev Dis Primers. 2018 Oct 1;4(1):27. doi: 10.1038/s41572-018-0025-4.
7
A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission.一类新型的内质网膜蛋白调控内质网相关内体分裂。
Cell. 2018 Sep 20;175(1):254-265.e14. doi: 10.1016/j.cell.2018.08.030. Epub 2018 Sep 13.
8
Iron overload is accompanied by mitochondrial and lysosomal dysfunction in WDR45 mutant cells.铁过载伴随着 WDR45 突变细胞中线粒体和溶酶体功能障碍。
Brain. 2018 Oct 1;141(10):3052-3064. doi: 10.1093/brain/awy230.
9
Mitochondrial dysfunction and mitophagy defect triggered by heterozygous GBA mutations.杂合 GBA 突变引发的线粒体功能障碍和自噬缺陷。
Autophagy. 2019 Jan;15(1):113-130. doi: 10.1080/15548627.2018.1509818. Epub 2018 Oct 12.
10
VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites.VPS13A 和 VPS13C 是脂质转运蛋白，在 ER 接触位点有不同的定位。
J Cell Biol. 2018 Oct 1;217(10):3625-3639. doi: 10.1083/jcb.201807019. Epub 2018 Aug 9.
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