线粒体是真核细胞中普遍存在的细胞器，主要负责调节细胞能量代谢、自由基生成和凋亡途径的执行。反常的 氧化磷酸化和有氧代谢是线粒体功能障碍的结果，被认为与肿瘤发生、发展有关。在过去的几十年里，肿瘤细胞 mtDNA 编码和控制区突变已经进行了广泛研究并已得到确认，突显 mtDNA 突变积累是引发持续的线粒体缺陷的一个关键因素， 并与肿瘤发生、发展密切相关。然而，这些 mtDNA 突变在肿瘤发生、发展过程中所发挥的作用仍然知之甚少。本文概 述了肿瘤中发现的多种细胞 mtDNA 突变，并着重介绍了在肿瘤转化和进展中 mtDNA 突变的因果关系，还扼要说明了 mtDNA 突变是如何激活线粒体 - 细胞核逆行信号，从而调节相关核基因的表达或诱导表观遗传变化，并促进肿瘤细胞的恶 性表型。根据目前研究成果，mtDNA 突变可以作为肿瘤早期诊断的一个生物学标记，也有望成为肿瘤治疗的潜在靶点， 但仍需进一步研究 mtDNA 在肿瘤中特定突变的功能和意义。

Mitochondria are ubiquitous organelles in eukaryotic cells, which are mainly responsible for the regulation cellular energy metabolism, generation of free radical, and the execution of apoptotic pathways. Abnormal oxidative phosphorylation and aerobic metabolism are the result of mitochondrial dysfunction and are thought to be involved in tumorigenesis. In the past decades, numerous mutations in both the coding and control regions of mitochondrial DNA (mtDNA) have been extensively examined and confirmed in a broad range of primary human cancer, underscoring that accumulation of mtDNA alterations may be a critical factor in eliciting persistent mitochondrial defects and consequently contribute to cancer initiation and progression. However, the roles of these mtDNA mutations in the carcinogenic process remain largely unknown. This review outlines a wide variety of mtDNA mutations identified in common human malignancies and highlighted recent advances in understanding the causal roles of mtDNA variations in neoplastic transformation and tumor progression. In addition, it briefly illustrates how mtDNA alterations activate mitochondriato-nucleus retrograde signaling so as to modulate the expression of relevant nuclear genes or induce epigenetic changes and promote malignant phenotypes in cancer cells. These findings strongly indicates that mtDNA mutations could be used as a diagnostic biomarker for early detection of cancer and as a potential target for the therapy of cancer, but continued investigations are definitely required to further elucidate the functional significance of specific mtDNA mutations in cancer.