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.
Stemmler
Timothy L
TL
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, France.
Lesuisse
Emmanuel
E
Laboratoire Mitochondrie, Metaux et Stress Oxydant, Institut Jacques Monod, CNRS-Universite Paris Diderot, 75205 Paris, France.
Pain
Debkumar
D
Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07101.
Dancis
Andrew
A
Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104. Electronic address: adancis@mail.med.upenn.edu.
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