Iron metabolism and ferroptosis in health and diseases: the crucial role of mitochondria in meta-bolically active tissues

Iron is essential in various physiological processes, but its accumulation leads to oxidative stress and cell damage, thus iron homeostasis has to be tightly regulated. Ferroptosis is an iron-dependent non-apoptotic regulated cell death characterized by iron overload and ROS accumulation. Mitochondria are organelles playing a crucial role in iron metabolism and involved in ferroptosis. MitoNEET, a protein of mitochondrial outer membrane, is a key element in this process. Ferroptosis, altering iron levels in several metabolically active organs, is linked to several non-communicable diseases. For example, iron overload in the liver leads to hepatic fibrosis and cirrhosis, accelerating NAFLD progression, in the muscle cells contributes to oxidative damage leading to sarcopenia, and in the brain is associated to neurodegeneration. The aim of this review is to investigate the intricate balance of iron regulation focusing on the role of mitochondria and oxidative stress, and analyzing the ferroptosis implications in health and disease.