Department of Biology, School of Science, Jacksonville State University, 700 Pelham Road North, Jacksonville, AL, 36265, USA.
Cell Biol Int. 2019 Nov;43(11):1323-1329. doi: 10.1002/cbin.11223. Epub 2019 Sep 8.
The life cycle of a cell is partly regulated by the programmed cell death (PCD) process. From development to demise, a cell's PCD process must respond to external signals and internal factors mediated by mitochondria. Previous studies show that the release of histones into the cytosol caused by DNA damage or loss of nuclear integrity is correlated with apoptosis in mammalian cells. These released histones bind to mitochondria and permeabilize its inner and outer membranes, which causes the release of cytochrome c into the cytosol that leads to caspase activation and the demise of the cell. Owing to the high conservation of histones, we hypothesize that histone-mediated cytochrome c release from mitochondria may be conserved across a wide range of eukaryotes. We investigated this histone-mitochondrial interaction in cauliflower using density-gradient purified mitochondria and exogenous histones from a crude histone fraction, then added the exogenous histone fractions to the purified cauliflower mitochondria and analyzed the mitochondrial pellets and supernatants by immunoblotting against cytochrome c and H3. Our data clearly shows that histone-enriched fractions elicited cytochrome c release from mitochondria, and that mitochondria bind exogenous histone H3.
细胞的生命周期部分受程序性细胞死亡 (PCD) 过程的调节。从发育到死亡，细胞的 PCD 过程必须响应由线粒体介导的外部信号和内部因素。先前的研究表明，哺乳动物细胞中由 DNA 损伤或核完整性丧失引起的组蛋白向细胞质中的释放与细胞凋亡有关。这些释放的组蛋白与线粒体结合并使内外膜通透，导致细胞色素 c 释放到细胞质中，从而激活半胱天冬酶并导致细胞死亡。由于组蛋白高度保守，我们假设组蛋白介导的线粒体细胞色素 c 释放可能在广泛的真核生物中保守。我们使用密度梯度纯化的线粒体和来自粗组蛋白部分的外源性组蛋白在花椰菜中研究了这种组蛋白-线粒体相互作用，然后将外源性组蛋白部分添加到纯化的花椰菜线粒体中，并通过针对细胞色素 c 和 H3 的免疫印迹分析线粒体沉淀和上清液。我们的数据清楚地表明，富含组蛋白的级分可从线粒体中引发细胞色素 c 的释放，并且线粒体结合外源性组蛋白 H3。
