Mitochondria-targeted compounds in the treatment of cancer

Mitochondria are highly dynamic organelles involved in many cellular functions. Beyond their central role in metabolism, they also take a part in maintaining calcium homeostasis, cell death, immunity, and ROS production. Changes in these functions have been shown to be crucial for the adaptation and survival of cancer cells. Mitochondria, therefore, constitute a promising target for the development of novel anticancer agents. The triphenylphosphonium (TPP+) moiety has been widely used to target molecules into mitochondria. TPP+ derivatives of a variety of conventional cytostatic drugs, natural substances, metformin, antioxidants or a range of newly synthesized molecules have shown promising results against cancer cells. In this review, we discuss biochemical differences between cancer cells and normal cells with a specific focus on mitochondria, and how mitochondrially targeted molecules can be used to selectively affect mitochondrial function in normal and cancer cells. We summarize the published data on mitochondrially targeted anticancer agents and propose future research avenues.