Mitochondrial Dysfunctions and Altered Metals Homeostasis: New Weapons to Counteract HCV-Related Oxidative Stress

Figure 1

Molecular mechanisms through which HCV induces mitochondrial damage and the consequent increased ROS production. Several HCV proteins associate with both endoplasmic reticulum (ER) and mitochondria. In particular, Core localizes also on MAMs and may play a role in the increase of mitochondrial Ca⁺⁺ pool, which in turn is involved in mitochondrial permeability transition pore (mPTP) opening, release of cytochrome c (Cyt C), and consequent mitochondrial depolarization. Organelle depolarization may be responsible for electron transport chain (ETC) failure and reactive oxygen species (ROS) overproduction. Enhanced ROS, in turn, may cause a further mPTP opening (dashed line), worsening the mitochondrial depolarization, thus leading to the onset of a vicious deleterious circle that aggravates the mitochondrial damage. Furthermore, some reports indicate that Complexes I and IV (CI and CIV, resp.) of the ETC are main targets of HCV actions. The fall of their activities plays key role in ETC failure and increased ROS production.