Review: mitochondrial defects in breast cancer

Abstract

Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of its high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Breast cancer is the most frequent cancer type among women in the world and, although exhaustive research has been done on nuclear DNA changes, several studies describe a variety of mitochondrial DNA alterations present in breast cancer. In this review article, we to provide a summary of the mitochondrial genomic alterations reported in breast cancer and their functional consequences.

Keywords: breast cancer; heteroplasmy; mitochondrial DNA; mutations.

Figure 1

mtDNA point mutations in breast cancer described in the literature. Every tick represents a mutation locus detected. Abbreviations: 12S: 12S ribosomal RNA; 16S: 16S ribosomal RNA; ND1, 2, 4, 5 and 6: NADH dehydrogenase subunit 1, 2, 4, 5 and 6; ATPase: ATP Synthase F0 subunit 8; COI, II and III: cytochrome c oxidase subunit I, II and III; Cyt B: cytochrome b; O_H: H-strand replication origin; O_L: L-strand replication origin.

Figure 2

The classic selection method used to explain the expansion of mtDNA homoplasmy in tumors (in the random genetic drift, human tumors are expected to contain homoplasmic mitochondrial mutations based only on random mutagenesis and segregation of mtDNA).