Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA.
Cancer Prev Res (Phila). 2011 May;4(5):638-54. doi: 10.1158/1940-6207.CAPR-10-0326.
Mitochondria control essential cellular activities including generation of ATP via oxidative phosphorylation. Mitochondrial DNA (mtDNA) mutations in the regulatory D-loop region and somatic mtDNA mutations are common in primary human cancers. The biological impact of a given mutation may vary, depending on the nature of the mutation and the proportion of mutant mtDNAs carried by the cell. Identification of mtDNA mutations in precancerous lesions supports their early contribution to cell transformation and cancer progression. Introduction of mtDNA mutations in transformed cells has been associated with increased ROS production and tumor growth. Studies reveal that increased and altered mtDNA plays a role in the development of cancer but further work is required to establish the functional significance of specific mitochondrial mutations in cancer and disease progression. This review offers some insight into the extent of mtDNA mutations, their functional consequences in tumorigenesis, mitochondrial therapeutics, and future clinical application.
线粒体控制着包括通过氧化磷酸化产生 ATP 在内的基本细胞活动。调节区 D-环的线粒体 DNA (mtDNA) 突变和体细胞 mtDNA 突变在原发性人类癌症中很常见。给定突变的生物学影响可能因突变的性质和细胞携带的突变 mtDNA 的比例而异。在癌前病变中检测到 mtDNA 突变支持它们对细胞转化和癌症进展的早期贡献。在转化细胞中引入 mtDNA 突变与增加的 ROS 产生和肿瘤生长有关。研究表明，增加和改变的 mtDNA 在癌症的发展中起作用，但需要进一步的工作来确定特定线粒体突变在癌症和疾病进展中的功能意义。这篇综述提供了一些关于 mtDNA 突变的程度、它们在肿瘤发生中的功能后果、线粒体治疗以及未来临床应用的见解。
