Frataxin and mitochondrial FeS cluster biogenesis.
Friedreich ataxia is an inherited neurodegenerative disease caused by frataxin deficiency. Frataxin is a conserved mitochondrial protein that plays a role in FeS cluster assembly in mitochondria. FeS clusters are modular cofactors that perform essential functions throughout the cell. They are synthesized by a multistep and multisubunit mitochondrial machinery that includes the scaffold protein Isu for assembling a protein-bound FeS cluster intermediate. Frataxin interacts with Isu, iron, and the cysteine desulfurase Nfs1, which supplies sulfide, thus placing it at the center of mitochondrial FeS cluster biosynthesis.
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, France.
Timothy L
TL
Stemmler
Laboratoire Mitochondrie, Metaux et Stress Oxydant, Institut Jacques Monod, CNRS-Universite Paris Diderot, 75205 Paris, France.
Emmanuel
E
Lesuisse
Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101.
Debkumar
D
Pain
Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104. Electronic address: adancis@mail.med.upenn.edu.
Andrew
A
Dancis
D000818:Animals; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism; D005621:Friedreich Ataxia / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D013440:Sulfides / Q000378:metabolism*; D000096923:Frataxin
D013437:Carbon-Sulfur Lyases; D007501:Iron; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D013440:Sulfides; D000096923:Frataxin; C513492:NFS1 protein, human