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Publication : ISCA1 is essential for mitochondrial Fe<sub>4</sub>S<sub>4</sub> biogenesis in vivo.

First Author  Beilschmidt LK Year  2017
Journal  Nat Commun Volume  8
Pages  15124 PubMed ID  28492233
Mgi Jnum  J:250557 Mgi Id  MGI:5920182
Doi  10.1038/ncomms15124 Citation  Beilschmidt LK, et al. (2017) ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo. Nat Commun 8:15124
abstractText  Mammalian A-type proteins, ISCA1 and ISCA2, are evolutionarily conserved proteins involved in iron-sulfur cluster (Fe-S) biogenesis. Recently, it was shown that ISCA1 and ISCA2 form a heterocomplex that is implicated in the maturation of mitochondrial Fe4S4 proteins. Here we report that mouse ISCA1 and ISCA2 are Fe2S2-containing proteins that combine all features of Fe-S carrier proteins. We use biochemical, spectroscopic and in vivo approaches to demonstrate that despite forming a complex, ISCA1 and ISCA2 establish discrete interactions with components of the late Fe-S machinery. Surprisingly, knockdown experiments in mouse skeletal muscle and in primary cultures of neurons suggest that ISCA1, but not ISCA2, is required for mitochondrial Fe4S4 proteins biogenesis. Collectively, our data suggest that cellular processes with different requirements for ISCA1, ISCA2 and ISCA1-ISCA2 complex seem to exist.
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