Mitochondrial DNA instability in human cancers

SummaryRecently, a metabolic shift between the increased cytoplasmic glycolysis and decreased mitochondrial respiration in cellular energy production has been regarded as a biological hallmark for human cancers. As speculated by Warburg in the 1950s, respiratory complexes (i.e., mitochondria in modern terminology) were impaired or suppressed in human cancers, and such a defect may play an important role in the carcinogenesis and progression of human cancer. To appraise the mitochondrial defect, several researchers paid considerable attention to the role of mitochondrial DNA (mtDNA) alterations in multiple human cancers, and some results showed clinical significance. Generally, the way to analyze mtDNA alterations is mainly focused on the quantitative copy number changes and the qualitative displacement loop (D-loop) mutations. Based on the heteroplasmic to homoplasmic D310 mutation of D-loop and progressive increase of mtDNA copy number, the theory of cancer clonal expansion can be well explained from the viewpoint of mtDNA alteration. In conclusion, the role of mtDNA instability might be a good biological marker to correlate with carcinogenesis, disease progression, and drug resistance in several human cancers.