Adrenodoxin: The archetype of vertebrate-type [2Fe–2S] cluster ferredoxins

Adrenodoxin is probably the best characterized member of the vertebrate-type [2Fe–2S]-cluster ferredoxins. It has been in the spotlight of scientific interest for many years due to its essential role in mammalian steroid hormone biosynthesis, where it acts as electron mediator between the NADPH-dependent adrenodoxin reductase and several mitochondrial cytochromes P450. In this review we will focus on the present knowledge about protein–protein recognition in the mitochondrial cytochrome P450 system and the modulation of the electron transfer between Adx and its redox partners, AdR and CYP(s). We also intend to point out the potential biotechnological applications of Adx as a versatile electron donor to different cytochromes P450, both in vitro and in vivo. Finally we will address the comparison between the mammalian cytochrome P450-associated adrenodoxin and ferredoxins involved in iron–sulfur-cluster biosynthesis. Despite their different functions, these proteins display an amazing similarity regarding their primary sequence, tertiary structure and biophysical features.