Effects of hexavalent chromium on mitochondria and their implications in carcinogenesis

Hexavalent chromium (Cr(VI)) is a well-known occupational and environmental human carcinogen. The cellular effect of Cr(VI) is complex and often nonspecific due to its ability to modulate multiple cellular targets. The toxicity of Cr(VI) is strongly linked to the generation of reactive oxygen species (ROS) during its reduction process. ROS can cause oxidation of cellular macromolecules, such as proteins, lipids, and DNA, thereby altering their functions. A major genotoxic effect of Cr(VI) that contributes to carcinogenesis is the formation of DNA adducts, which can lead to DNA damage. Modulations of cellular signaling pathways and epigenetics may also contribute to the carcinogenic effects of Cr(VI). Cr(VI) has a major impact on many aspects of mitochondrial biology, including oxidative phosphorylation, mitophagy, and mitochondrial biogenesis. These effects have the potential to alter the trajectory of Cr(VI)-induced carcinogenic process. This perspective article summarizes current understandings of the effect of Cr(VI) on mitochondria and discusses the future directions of research in this area, particularly with regard to carcinogenesis.