New Roles of Mitochondrial Transcription Factor A in Cancer

Abstract

Mitochondria are the main sites of energy production in almost all eukaryotic cells. Mitochondria use oxidative phosphorylation to convert redox energy of substrates into adenosine triphosphate (ATP). Mitochondrial transcription factor A (mtTFA; also known as TFAM) is necessary for both transcription and maintenance of mitochondrial DNA (mtDNA), and it is one of the high mobility group (HMG) proteins that preferentially recognizes cisplatin-damaged DNA and oxidized DNA. Loss of mtTFA causes depletion of mtDNA, loss of mitochondrial transcripts, loss of mtDNA-encoded polypeptides, and severe respiratory chain deficiency. Mitochondria play a critical role in cancer cell metabolism and are also essential for cell proliferation. It is well known that mitochondrial uncoupling mediates the metabolic shift to aerobic glycolysis in cancer cells. Thus, mitochondria control cell survival and growth. In addition, the number of mitochondria correlates with the growth rate of cancer cells. The information gleaned from this review may provide critical clues to novel therapeutic interventions aimed at overcoming cancer. More detailed functional analyses of mtTFA should further elucidate its role in mitochondrial genome instability and apoptosis.c