Mammalian iron–sulfur cluster biogenesis: Recent insights into the roles of frataxin, acyl carrier protein and ATPase-mediated transfer to recipient proteins

Nunziata Maio, Anshika Jain, Tracey A. Rouault; Current Opinion in Chemical Biology, Volume 55, 2020, Pages 34-44, doi:10.1016/j.cbpa.2019.11.014.

Highlights:

Iron–sulfur (Fe–S) clusters (ISCs) are metal cofactors involved in multiple, essential cellular processes.
Defined pathways assemble ISCs de novo in mammalian mitochondria and cytosol.
The acyl carrier protein is a component of the core ISC machinery.
Frataxin is an allosteric regulator that accelerates sulfur transfer from NFS1 to ISCU.
A chaperone/cochaperone system facilitates cluster transfer downstream of ISCU.

Insights into the role of FXN in FeeS biogenesis have arisen from recent structural and biochemical studies, an important future direction will be to search for drugs that can mimic FXN activity to treat patients with Friedreich’s ataxia, a disease caused by low FXN expression. The source of iron for Fe-S biogenesis remains unsettled, and future work will likely focus on how iron is delivered to the Fe-S biogenesis machinery. Much progress has been made, but many basic questions remain unanswered in the complex process of mammalian Fe-S biogenesis

Mammalian iron–sulfur cluster biogenesis: Recent insights into the roles of frataxin, acyl carrier protein and ATPase-mediated transfer to recipient proteins