Cancer is a heterogeneous set of diseases characterized by different molecular and cellular features. Over the past decades, researchers have attempted to grasp the complexity of cancer by mapping the genetic aberrations associated with it. In these efforts, the contribution of mitochondria to the pathogenesis of cancer has tended to be neglected. However, more recently, a growing body of evidence suggests that mitochondria play a key role in cancer. In fact, dysfunctional mitochondria not only contribute to the metabolic reprogramming of cancer cells but they also modulate a plethora of cellular processes involved in tumorigenesis. In this review, we describe the link between mutations to mitochondrial enzymes and tumor formation. We also discuss the hypothesis that mutations to mitochondrial and nuclear DNA could cooperate to promote the survival of cancer cells in an evolving metabolic landscape.
Keywords: Cancer; Evolution; Metabolism; Mitochondria; Oncometabolites; TCA cycle; mtDNA mutations.