Doğan Nazlı, Çoban Neslihan
Istanbul University, Aziz Sancar Experimental Medicine Research Institute, Department of Genetics, Istanbul, Türkiye.
Istanbul University, Institute of Health Sciences, Istanbul, Türkiye.
Turk Kardiyol Dern Ars. 2023 Mar;51(2):135-145. doi: 10.5543/tkda.2022.39448.
Mitochondria are cell organelles that play an important role in various cellular processes, especially in aerobic respiration and energy production. Although it has its own genome, the mitochondrial genome does not encode all of the proteins necessary for the mitochondria to function. Nuclear genome is needed for increased mitochondrial number, metabolic activities associated with mitochondria, and replication of mitochondrial deoxyribonucleic acid. As a result of mitochondria dysfunction in cells, oxidative stress occurs with the formation of reactive oxygen species, a product of oxidative metabolism, and the oxidant/antioxidant imbalance. Reactive oxygen species damage cellular molecules such as proteins, ribonucleic acid, deoxyribonucleic acid, and mitochondrial deoxyribonucleic acid under the conditions of oxidative stress. Molecular changes as a result of the reactive oxygen species cause the loss of mitochondria function, resulting in an increased number of dysfunctional mitochondria. Thus, the loss of function of mitochondria and defects in oxidative metabolism increase the formation of reactive oxygen species and cause an increase in mutations in mitochondrial deoxyribonucleic acid. These results also affect mitochondrial biogenesis and accelerate the formation of multifactorial diseases as a result of the decrease in the number of functional mitochondria. In addition, microribonucleic acids, one of the epigenetic regulators, regulate nuclear and mitochondrial genes that control mitochondrial functions. Mitochondrial deoxyribonucleic acid mutated with reactive oxygen species, altered nuclear genome regulators and micro-ribonucleic acids, have been associated with various diseases mediated by mitochondrial dysfunction, including aging and coronary artery disease.
线粒体是在各种细胞过程中发挥重要作用的细胞器，尤其是在有氧呼吸和能量产生方面。尽管线粒体有自己的基因组，但线粒体基因组并不编码线粒体发挥功能所需的所有蛋白质。线粒体数量的增加、与线粒体相关的代谢活动以及线粒体脱氧核糖核酸的复制都需要核基因组。由于细胞中的线粒体功能障碍，会产生氧化应激，形成活性氧（氧化代谢的产物），导致氧化剂/抗氧化剂失衡。在氧化应激条件下，活性氧会损伤细胞分子，如蛋白质、核糖核酸、脱氧核糖核酸和线粒体脱氧核糖核酸。活性氧导致的分子变化会使线粒体功能丧失，导致功能失调的线粒体数量增加。因此，线粒体功能丧失和氧化代谢缺陷会增加活性氧的形成，并导致线粒体脱氧核糖核酸突变增加。这些结果也会影响线粒体生物合成，并由于功能性线粒体数量减少而加速多因素疾病的形成。此外，作为表观遗传调节因子之一的微小核糖核酸，可调节控制线粒体功能的核基因和线粒体基因。因活性氧而发生突变的线粒体脱氧核糖核酸、改变的核基因组调节因子和微小核糖核酸，都与包括衰老和冠状动脉疾病在内的多种由线粒体功能障碍介导的疾病有关。
