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纺锤体微管组织中心的非对称遗传可延长复制寿命。

Asymmetric inheritance of spindle microtubule-organizing centres preserves replicative lifespan.

机构信息

Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Spanish National Research Council (CSIC), University of Seville, University Pablo de Olavide, Sevilla, Spain.

出版信息

Nat Cell Biol. 2019 Aug;21(8):952-965. doi: 10.1038/s41556-019-0364-8. Epub 2019 Jul 29.

Abstract

The differential distribution of the microtubule-organizing centres (MTOCs) that orchestrate spindle formation during cell division is a fascinating phenomenon originally described in Saccharomyces cerevisiae and later found to be conserved during stem cell divisions in organisms ranging from Drosophila to humans. Whether predetermined MTOC inheritance patterns fulfil any biological function is however unknown. Using a genetically designed S. cerevisiae strain that displays a constitutively inverted MTOC fate, we demonstrate that the asymmetric segregation of these structures is critical to ensure normal levels of the Sir2 sirtuin and correct localization of the mitochondrial inheritance regulator Mfb1, and therefore to properly distribute functional mitochondria and protein aggregates between the mother and daughter cells. Consequently, interfering with this process severely accelerates cellular ageing.

摘要

微管组织中心(MTOC)的差异分布在细胞分裂过程中协调纺锤体的形成,这是一个令人着迷的现象,最初在酿酒酵母中描述,后来在从果蝇到人类的生物体的干细胞分裂中发现保守。然而,预定的 MTOC 遗传模式是否具有任何生物学功能尚不清楚。我们使用一种经过基因设计的酿酒酵母菌株,该菌株显示出组成型倒置的 MTOC 命运,证明了这些结构的不对称分离对于确保 Sir2 沉默酶和线粒体遗传调节剂 Mfb1 的正确定位的正常水平至关重要,从而正确分配功能线粒体和蛋白质聚集体在母细胞和子细胞之间。因此,干扰这个过程会严重加速细胞衰老。

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