Intracellular and microenvironmental regulation of mitochondrial membrane potential in cancer cells

Cancer cells have an abnormally high mitochondrial membrane potential (ΔΨ_m ), which is associated with enhanced invasive properties in vitro and increased metastases in vivo. The mechanisms underlying the abnormal ΔΨ_m in cancer cells remain unclear. Research on different cell types has shown that ΔΨ_m is regulated by various intracellular mechanisms such as by mitochondrial inner and outer membrane ion transporters, cytoskeletal elements, and biochemical signaling pathways. On the other hand, the role of extrinsic, tumor microenvironment (TME) derived cues in regulating ΔΨ_m is not well defined. In this review, we first summarize the existing literature on intercellular mechanisms of ΔΨ_m regulation, with a focus on cancer cells. We then offer our perspective on the different ways through which the microenvironmental cues such as hypoxia and mechanical stresses may regulate cancer cell ΔΨ_m . This article is categorized under: Cancer > Environmental Factors Cancer > Biomedical Engineering Cancer > Molecular and Cellular Physiology.