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在线粒体中，β-肌动蛋白调节线粒体DNA转录，是线粒体质量控制所必需的。

In Mitochondria ?-Actin Regulates mtDNA Transcription and Is Required for Mitochondrial Quality Control.

作者信息

Xie Xin, Venit Tomas, Drou Nizar, Percipalle Piergiorgio

机构信息

Science Division, Biology Program, New York University Abu Dhabi (NYUAD), P.O. Box 129188, Abu Dhabi, United Arab Emirates.

NYU Abu Dhabi Center for Genomics and Systems Biology, Abu Dhabi, UAE.

出版信息

iScience. 2018 May 25;3:226-237. doi: 10.1016/j.isci.2018.04.021. Epub 2018 May 3.

DOI:10.1016/j.isci.2018.04.021
PMID:30428323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6137402/
Abstract

In eukaryotic cells, actin regulates both cytoplasmic and nuclear functions. However, whether actin-based structures are present in the mitochondria and are involved in mitochondrial functions has not been investigated. Here, using wild-type ?-actin +/+ and knockout (KO) ?-actin ?/? mouse embryonic fibroblasts we show evidence for the defect in maintaining mitochondrial membrane potential (MMP) in ?-actin-null cells. MMP defects were associated with impaired mitochondrial DNA (mtDNA) transcription and nuclear oxidative phosphorylation (OXPHOS) gene expression. Using super-resolution microscopy we provided direct evidence on the presence of ?-actin-containing structures inside mitochondria. Large aggregates of TFAM-stained nucleoids were observed in bulb-shaped mitochondria in KO cells, suggesting defects in mitochondrial nucleoid segregation without ?-actin. The observation that mitochondria-targeted ?-actin rescued mtDNA transcription and MMP suggests an indispensable functional role of a mitochondrial ?-actin pool necessary for mitochondrial quality control.

摘要

在真核细胞中，肌动蛋白调节细胞质和细胞核功能。然而，基于肌动蛋白的结构是否存在于线粒体中以及是否参与线粒体功能尚未得到研究。在这里，我们使用野生型α-肌动蛋白+/+和基因敲除（KO）α-肌动蛋白-/-小鼠胚胎成纤维细胞，证明了α-肌动蛋白缺失细胞在维持线粒体膜电位（MMP）方面存在缺陷。MMP缺陷与线粒体DNA（mtDNA）转录受损和核氧化磷酸化（OXPHOS）基因表达受损有关。使用超分辨率显微镜，我们提供了线粒体内部存在含α-肌动蛋白结构的直接证据。在KO细胞的球状线粒体中观察到大量经TFAM染色的类核聚集体，表明缺乏α-肌动蛋白时线粒体类核分离存在缺陷。靶向线粒体的α-肌动蛋白可挽救mtDNA转录和MMP这一观察结果表明，线粒体α-肌动蛋白库对于线粒体质量控制具有不可或缺的功能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/aff61de66c6e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/e646b0e79f11/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/fa5dec416565/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/68c880937407/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/bc9d26191707/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/aff61de66c6e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/e646b0e79f11/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/fa5dec416565/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/68c880937407/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/bc9d26191707/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a38/6137402/aff61de66c6e/gr4.jpg

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