Role of apoptosis-inducing factor (AIF) in programmed nuclear death during conjugation in Tetrahymena thermophila.
Role of apoptosis-inducing factor (AIF) in programmed nuclear death during conjugation in Tetrahymena thermophila.
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DOI：
10.1186/1471-2121-11-13
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发表时间：
2010-02-11
期刊：
影响因子：
--
通讯作者：
Endoh H
中科院分区：
文献类型：
--
作者：
Akematsu T;Endoh H
程序性核死亡(PND)，也被称为核凋亡，是纤毛虫在有性繁殖(接合)过程中发生的一种显著的过程。在嗜热四膜虫中，当新的大核分化时，亲代大核被选择性地从后代的细胞质中消除，伴随着凋亡的核事件。然而，这些事件背后的分子机制还不是很清楚。亲代大核被一个大的自噬小体吞噬，其中包含许多失去膜电位的线粒体。在动物中，线粒体去极化先于凋亡细胞死亡，这涉及DNA片段化和随后的核降解。我们重点研究了线粒体凋亡诱导因子(AIF)在四膜虫PND过程中的作用。AIF的破坏延缓了PND的正常进展，特别是核固缩和千碱基大小的DNA碎裂。AIF定位于四膜虫线粒体，在核凝聚之前被释放到大核中。此外，AIF与线粒体DNA酶结合并协同作用，促进千碱基大小的DNA降解，随后是寡核小体大小的DNA阶梯。我们的结果表明，四膜虫AIF在PND早期的DNA降解过程中起着重要作用，这支持了线粒体启动的DNA降解途径在真核生物中广泛保守的观点。
Programmed nuclear death (PND), which is also referred to as nuclear apoptosis, is a remarkable process that occurs in ciliates during sexual reproduction (conjugation). In Tetrahymena thermophila, when the new macronucleus differentiates, the parental macronucleus is selectively eliminated from the cytoplasm of the progeny, concomitant with apoptotic nuclear events. However, the molecular mechanisms underlying these events are not well understood. The parental macronucleus is engulfed by a large autophagosome, which contains numerous mitochondria that have lost their membrane potential. In animals, mitochondrial depolarization precedes apoptotic cell death, which involves DNA fragmentation and subsequent nuclear degradation. We focused on the role of mitochondrial apoptosis-inducing factor (AIF) during PND in Tetrahymena. The disruption of AIF delays the normal progression of PND, specifically, nuclear condensation and kilobase-size DNA fragmentation. AIF is localized in Tetrahymena mitochondria and is released into the macronucleus prior to nuclear condensation. In addition, AIF associates and co-operates with the mitochondrial DNase to facilitate the degradation of kilobase-size DNA, which is followed by oligonucleosome-size DNA laddering. Our results suggest that Tetrahymena AIF plays an important role in the degradation of DNA at an early stage of PND, which supports the notion that the mitochondrion-initiated apoptotic DNA degradation pathway is widely conserved among eukaryotes.
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