Figure 1.

Hyperestrogenism and mitochondrial dysfunction in type I endometrial cancer. Hyperestrogenism may stimulate reactive oxygen species (ROS) production and increase mitochondrial biogenesis. ROS increase and excessive mitochondrial DNA (mtDNA) replication due to increased mitochondrial biogenesis may lead to mtDNA mutations. These mutations may affect respiratory complexes, in particular complex I, and may induce mitochondrial dysfunction that reinforces ROS production and stimulates mitochondrial proliferation in a vicious cycle. ROS increase activates the antioxidant response. Mitochondrial dysfunction may also increase mitochondrial fission in order to segregate damaged mitochondria components, which can then be degraded by proteolysis and mitophagy.