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线粒体动力学调控——子囊菌波氏假丝酵母中融合与裂变基因的特征分析

Regulation of mitochondrial dynamics--characterization of fusion and fission genes in the ascomycete Podospora anserina.

作者信息

Scheckhuber Christian Q, Rödel Elfie, Wüstehube Joycelyn

机构信息

Johann W. Goethe-Universität, Institut für Molekulare Biowissenschaften, Frankfurt am Main, Germany.

出版信息

Biotechnol J. 2008 Jun;3(6):781-90. doi: 10.1002/biot.200800010.

Abstract

The filamentous ascomycete Podospora anserina is a model system for studying aging, a complex process that is regulated by multiple factors. Among these, mitochondria were shown to be of crucial importance. Recently, it was shown that the morphology of these organelles, which is dependent on dynamic fusion and fission processes, has profound effects on P. anserina aging. To further analyze this phenomenon, we characterized molecular components of the machinery regulating the dynamic behavior of mitochondria by utilizing transgenic strains in which fission genes (PaDnm1, PaFis1 and PaMdv1) and a fusion gene (PaFzo1) are overexpressed. While overexpression of PaFis1 has no phenotypic effects in the genetic background of the wild type, it surprisingly promotes mitochondrial fusion and decreases the life span in a mutant overexpressing PaDnm1. Remarkably, when grown on synthetic medium, overexpression of PaDnm1 leads to a decreased life span compared to the wild type. Increased expression of PaMdv1 results in the formation of ring-shaped mitochondria, a morphology of these organelles that has not been previously observed in P. anserina. Transformants with elevated PaFzo1 transcript levels show no altered life span, although the age-dependent fragmentation of mitochondria is impaired.

摘要

丝状子囊菌嗜热栖热孢霉是研究衰老的模型系统,衰老是一个受多种因素调控的复杂过程。其中,线粒体被证明至关重要。最近发现,这些细胞器的形态依赖于动态融合和裂变过程,对嗜热栖热孢霉的衰老有深远影响。为了进一步分析这一现象,我们利用转基因菌株对调控线粒体动态行为的分子机制进行了表征,在这些转基因菌株中,裂变基因(PaDnm1、PaFis1和PaMdv1)和一个融合基因(PaFzo1)过表达。虽然在野生型遗传背景下,PaFis1的过表达没有表型效应,但令人惊讶的是,在过表达PaDnm1的突变体中,它促进了线粒体融合并缩短了寿命。值得注意的是,在合成培养基上生长时,与野生型相比,PaDnm1的过表达导致寿命缩短。PaMdv1表达的增加导致形成环形线粒体,这种细胞器形态在嗜热栖热孢霉中以前未曾观察到。尽管线粒体随年龄增长的碎片化受到损害,但PaFzo1转录水平升高的转化体的寿命没有改变。

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