异性染色素表皮造会导致线粒体功能障碍,从而产生抗真菌耐药性
Andreas Fellas1,2, Alison L Pidoux3, Pin Tong1
1Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, EH9 3BF, Scotland, UK.
The EMBO journal
|December 1, 2025
概括
裂变酵母使用可逆的表皮,导致线粒体功能障碍,以获得药物耐药性. 这些表观遗传变化,涉及基因组修饰,突出显示了一种潜在的驱动病原体抗真菌耐药性的保存机制.
科学领域:
- 表观遗传学和基因调控
- 线粒体生物学 线粒体生物学
- 抗真菌抵抗机制 抗真菌抵抗机制
背景情况:
- 抗真菌耐药性对全球健康和粮食安全构成重大威胁.
- 裂变酵母,Schizosaccharomyces pombe,表现出可逆的表皮,使其对各种压力因素具有抵抗力.
- 耐药的表在特定的基因位置上显示异性染色素岛屿,导致基因抑制.
研究的目的:
- 为了研究线粒体蛋白抑制通过异性染色素岛屿在赋予抗真菌耐药性的作用.
- 阐明分子机制,将线粒体功能障碍与裂变酵母中的耐药性联系起来.
- 探索病原性真菌中这种抵抗机制的潜在保护.
主要方法:
- 对裂变酵母经过异位基因组-H3K9甲基化而产生的生化酵母的分析.
- 基因操纵 (cup1-tt,ppr4Δ) 来模仿表位效应.
- 评估线粒体功能 (呼吸,生长,活性氧物种).
- 转录基因分析以确定激活的途径 (例如,Pap1转录因子).
主要成果:
- 线粒体基因Cup1和Ppr4通过异色素蛋白岛屿的抑制会产生抗性.
- 基因突变者 (cup1-tt,ppr4Δ) 呈现线粒体功能障碍和形表表.
- 线粒体功能障碍激活了Pap1的氧化应激反应和线粒细胞逆行通路,增加了排泄活动.
结论:
- 裂变酵母利用诱导线粒体功能障碍的表皮突变作为克服环境侮辱和药物暴露的战略.
- 观察到的机制,涉及色氨酸介导的基因沉默和随后的线粒体损伤,直接与耐药性有关.
- 这种由表皮转移驱动的线粒体功能障碍途径可能是促进致病真菌抗真菌耐药性的保存机制.
相关概念视频
02:38Heterochromatin
17.8K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
17.8K
03:17Inheritance of Chromatin Structures
7.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.2K
02:25Spreading of Chromatin Modifications
9.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
9.3K
01:37Epigenetic Regulation
3.7K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.7K
01:46Epigenetic Regulation
33.4K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.4K
02:32Position-effect Variegation
7.0K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
7.0K