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丝状伪足中成分独特的线粒体支持细胞迁移。

Compositionally unique mitochondria in filopodia support cellular migration.

作者信息

Marlar-Pavey Madeleine, Tapias-Gomez Daniel, Mettlen Marcel, Friedman Jonathan R

机构信息

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.

出版信息

bioRxiv. 2024 Jun 21:2024.06.21.600105. doi: 10.1101/2024.06.21.600105.

DOI:10.1101/2024.06.21.600105
PMID:38948746
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11212966/
Abstract

Local metabolic demand within cells varies widely and the extent to which individual mitochondria can be specialized to meet these functional needs is unclear. We examined the subcellular distribution of MICOS, a spatial and functional organizer of mitochondria, and discovered that it dynamically enriches at the tip of a minor population of mitochondria in the cell periphery that we term "METEORs". METEORs have a unique composition; MICOS enrichment sites are depleted of mtDNA and matrix proteins and contain high levels of the Ca uniporter MCU, suggesting a functional specialization. METEORs are also enriched for the myosin MYO19, which promotes their trafficking to a small subset of filopodia. We identify a positive correlation between the length of filopodia and the presence of METEORs and show that elimination of mitochondria from filopodia impairs cellular motility. Our data reveal a novel type of mitochondrial heterogeneity and suggest compositionally specialized mitochondria support cell migration.

摘要

细胞内局部代谢需求差异很大，而单个线粒体能够专门化以满足这些功能需求的程度尚不清楚。我们研究了线粒体的空间和功能组织者MICOS的亚细胞分布，发现它动态富集于细胞周边少数线粒体的尖端，我们将其称为“流星体”（METEORs）。流星体具有独特的组成；MICOS富集位点缺乏线粒体DNA和基质蛋白，且含有高水平的钙离子单向转运体MCU，这表明其具有功能特异性。流星体还富含肌球蛋白MYO19，后者促进它们向一小部分丝状伪足的运输。我们发现丝状伪足的长度与流星体的存在呈正相关，并表明从丝状伪足中去除线粒体损害细胞运动。我们的数据揭示了一种新型的线粒体异质性，并表明组成上专门化的线粒体支持细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/ac431602ed48/nihpp-2024.06.21.600105v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/e66b961a00a0/nihpp-2024.06.21.600105v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/eac1b1a96875/nihpp-2024.06.21.600105v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/bb8510bedd3f/nihpp-2024.06.21.600105v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/fbc19f621150/nihpp-2024.06.21.600105v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/ac431602ed48/nihpp-2024.06.21.600105v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/e66b961a00a0/nihpp-2024.06.21.600105v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/eac1b1a96875/nihpp-2024.06.21.600105v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/bb8510bedd3f/nihpp-2024.06.21.600105v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/fbc19f621150/nihpp-2024.06.21.600105v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afe/11212966/ac431602ed48/nihpp-2024.06.21.600105v1-f0005.jpg

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本文引用的文献

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Functionally conserved inner mitochondrial membrane proteins CCDC51 and Mdm33 demarcate a subset of fission events.功能保守的线粒体内膜蛋白CCDC51和Mdm33划分出了一部分裂变事件。
J Cell Biol. 2025 Mar 3;224(3). doi: 10.1083/jcb.202403140. Epub 2024 Dec 24.
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Mitochondria at the crossroads of health and disease.线粒体在健康与疾病的交汇点。
Cell. 2024 May 23;187(11):2601-2627. doi: 10.1016/j.cell.2024.04.037.
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Mitochondrial heterogeneity and adaptations to cellular needs.线粒体异质性与细胞需求的适应
Nat Cell Biol. 2024 May;26(5):674-686. doi: 10.1038/s41556-024-01410-1. Epub 2024 May 16.
4
A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.一种动力蛋白超家族样假酶与 MICOS 协同作用促进嵴结构。
Curr Biol. 2024 Jun 17;34(12):2606-2622.e9. doi: 10.1016/j.cub.2024.04.028. Epub 2024 Apr 30.
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Mitochondria in disease: changes in shapes and dynamics.线粒体在疾病中的作用：形态和动力学的变化。
Trends Biochem Sci. 2024 Apr;49(4):346-360. doi: 10.1016/j.tibs.2024.01.011. Epub 2024 Feb 23.
6
Mitochondrial-derived vesicles in metabolism, disease, and aging.线粒体衍生小泡在代谢、疾病和衰老中的作用。
Cell Metab. 2024 Jan 2;36(1):21-35. doi: 10.1016/j.cmet.2023.11.014.
7
Mitochondrial complexome and import network.线粒体复合物组和导入网络。
Trends Cell Biol. 2024 Jul;34(7):578-594. doi: 10.1016/j.tcb.2023.10.004. Epub 2023 Oct 31.
8
Filopodia In Vitro and In Vivo.丝状伪足的体外与体内研究
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