ISCA1 is essential for mitochondrial Fe₄S₄ biogenesis in vivo.

ABSTRACT: 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 Fe

SUBMITTER: Beilschmidt LK 

PROVIDER: S-EPMC5437272 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature