The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age.

Mitochondria decay with age from oxidative damage and loss of protective mechanisms. Resistance, repair, and replacement mechanisms are essential for mitochondrial preservation and maintenance. Iron plays an essential role in the maintenance of mitochondria, through its two major functional forms: heme and iron-sulfur clusters. Both iron-based cofactors are formed and utilized in the mitochondria and then distributed throughout the cell. This is an important function of mitochondria that is not directly related to the production of ATP. Heme and iron-sulfur clusters are important for the normal assembly and for the optimal activity of the electron transfer complexes. Loss of mitochondrial cytochrome c oxidase (complex IV), integrity of mtDNA, and function can result from abnormal homeostasis of iron. We review the physiological role of iron-sulfur clusters and heme in the integrity of the mitochondria and the generation of oxidants.