Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy

Abstract

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

Keywords: cancer chemotherapy; cisplatin; mtDNA; mtTFA; prognosis.

Figure 1

Cellular pathways and apoptosis induced by cisplatin. Cisplatin activates signal transduction pathways and may directly interact with mitochondria, which can induce apoptosis.

Figure 2

Cisplatin-induced signaling, cisplatin resistance and transcription system in cancer cells discussed in this review. mtTFA functions in both nuclei and mitochondria to not only interact with cisplatin-modified DNA, but also regulate the nuclear and mitochondrial gene expression.