FIGURE 4.

Metabolic reprogramming induced by copper in hematopoietic stem cells. Noncytotoxic copper overload induces both the complex IV assembly and ROS generation, which promote mitochondrial turnover and biogenesis. As a result, more active and oxidative mitochondria are produced, which promote cell differentiation in HSCs. A decrease in copper concentration will down regulate the expression of complex IV, making mitochondria less oxidative. Since mitochondria will not be able to satisfy energy demands, the energy metabolism switches to glycolysis, which in turn will promote cell proliferation (adapted from Jensen et al., 2019 and Ruiz et al., 2016).