Akematsu Takahiko, Endoh Hiroshi
Division of Life Science, Graduate School of Natural Science and Technology, Kanazawa University, Shizenken, Kakuma-machi, Kanazawa, Ishikawa, Japan.
BMC Cell Biol. 2010 Feb 11;11:13. doi: 10.1186/1471-2121-11-13.
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.
程序性核死亡（PND），也被称为核凋亡，是纤毛虫在有性生殖（接合生殖）过程中发生的一个显著过程。在嗜热四膜虫中，当新的大核分化时，亲代大核会从子代细胞质中被选择性清除，同时伴有凋亡性核事件。然而，这些事件背后的分子机制尚未完全了解。亲代大核被一个大型自噬体吞噬，该自噬体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性细胞死亡，这涉及DNA片段化及随后的核降解。
我们聚焦于线粒体凋亡诱导因子（AIF）在嗜热四膜虫PND过程中的作用。AIF的破坏会延迟PND的正常进程，具体而言，会延迟核浓缩和千碱基大小的DNA片段化。AIF定位于嗜热四膜虫的线粒体中，并在核浓缩之前释放到细胞核中。此外，AIF与线粒体DNA酶结合并协同作用，以促进千碱基大小的DNA降解，随后是寡核小体大小的DNA梯状条带形成。
我们的结果表明，嗜热四膜虫AIF在PND早期的DNA降解中起重要作用，这支持了线粒体启动的凋亡性DNA降解途径在真核生物中广泛保守的观点。
