The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities

Abstract

Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.

Keywords: DNA alteration; human cancer; mitochondria; mitochondrial genome; mtDNA.

Figure 1

Structure of the human mitochondrial genome. Colored boxes represent locations of D-loop (red), transfer RNAs (light gray), ribosomal RNAs (orange), Complex I NADH dehydrogenase genes (purple), Complex III cytochrome c reductase gene (yellow), Complex IV cytochrome c oxidase genes (blue), and Complex V adenosine triphosphate synthase genes (green). Boxes appearing shorter represent antisense transcripts; others are sense transcripts. Hypervariable regions (16) are represented by dark gray bars, the “common deletion” (17) as a pink bar, and the genes described in Abundance and Distribution of Mitochondrial Mutations as relevant to cancer are highlighted with black bars. Diagram created in Circos (18) from GenBank accession NC_012920 (revised Cambridge Reference Sequence); code available at https://github.com/k8hertweck/mt_genome_viz.