Fabian Fischer, Julian D. Langer & Heinz D. Osiewacz; (NATURE) Scientific Reports 5, Article number: 18375 (2015) doi:10.1038/srep18375
OPEN
Among the CLPP-associated pathologies is Friedreich’s Ataxia (FRDA), a neurodegenerative disease caused by failed assembly of Fe-S clusters due to defects in the mitochondrial iron chaperone frataxin31. In a FRDA mouse model, the proteolytic component CLPP is upregulated at mid-stage of the disease. This upregulation is concomitant with a loss of mitochondrial Fe-S proteins, indicating they are targets of CLPP in FRDA. Indeed, several proteins we identified in our study contain or bind to Fe-S clusters, e.g. aconitase, biotin synthase, and complex I components such as the NADH-ubiquinone oxidoreductase 75 kDa subunit. In addition, three of the proteins found as CLPXP interactors or substrates, the cysteine desulfurase NSF1, the chaperone HSPA9, and the glutaredoxin-related protein 5, are known to be essential for Fe-S cluster biogenesis in eukaryotic cells including those of mammals. Thus, our findings support the idea that CLPXP has a functional role in FRDA and might possibly be involved in regulating Fe-S cluster assembly and Fe-S cluster proteins.
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