有害的异质体线粒体突变与整体和癌症特异性死亡率的风险增加有关
Yun Soo Hong1, Stephanie L Battle1,2, Wen Shi1
1McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nature communications
|September 30, 2023
概括
线粒体DNA异质体与死亡风险增加1.5倍有关. 特定的线粒体变异也与癌症风险和死亡率相关,特别是白血病.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 老年学是一门学科.
背景情况:
- 线粒体拥有自己的基因组 (mtDNA),与核DNA不同.
- mtDNA变体可以存在于异质体中,具有不同比例的变异性DNA分子.
- 线粒体DNA的破坏与衰老和相关疾病有关.
研究的目的:
- 在一个大队伍中量化线粒体DNA异质体.
- 调查mtDNA异质体和变异与全因死亡率的关联.
- 探索mtDNA变异在癌症患病率,发病率和死亡率中的作用.
主要方法:
- 在194,871名英国生物库参与者中量化mtDNA异质体.
- 使用线粒体局部约束得分和值 (MSS) 对mtDNA单核酸变异 (SNVs) 的功能性表征.
- 统计分析以确定与死亡率和癌症结局的关联.
主要成果:
- mtDNA异质体与全因死亡风险增加1.5倍有关.
- 对于mtDNA SNVs的MSS得分显示了与全因死亡率的关联.
- mtDNA变异与癌症的患病率,发病率和死亡率有关,特别是白血病.
结论:
- 线粒体异质体是所有原因死亡的重要危险因素.
- mtDNA变异可能在某些癌症,特别是白血病的发展中发挥功能作用.
- 线粒体异质体SNV显示出潜在的癌症,特别是白血病的预后标志物.
相关概念视频
Animal Mitochondrial Genetics
7.6K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.6K
Mismatch Repair
4.9K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K
Mitochondria
13.7K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
13.7K
Mutations
83.4K
Overview
83.4K
Electron Transport Chain: Complex I and II
14.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.3K
Mitochondrial Membranes
11.4K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
11.4K


