ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo.

Lena Kristina Beilschmidt (1, 2) , Sandrine Ollagnier de Choudens (3) , Majorie Fournier (1, 4) , Ioannis Sanakis (5) , Marc-André Hograindleur (3) , Martin Clémancey (3) , Geneviève Blondin (3) , Stéphane Schmucker (1, 2) , Aurélie Eisenmann (1, 2) , Amélie Weiss (1) , Pascale Koebel (1) , Nadia Messaddeq (1) , Hélène Puccio (1, 2) , Alain Martelli (1, 2, 6)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 Collège de France - Chaire Génétique Humaine
3 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
4 Sir William Dunn School of Pathology [Oxford]
5 NCSR, Demokritos, Institut de Science des Matériaux
6 Rare Disease Research Unit, Pfizer Inc

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.

Domaines: Biochimie, Biologie Moléculaire; Biologie cellulaire

Lena Kristina Beilschmidt, Sandrine Ollagnier de Choudens, Majorie Fournier, Ioannis Sanakis, Marc-André Hograindleur, et al.. ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo.. Nature Communications, 2017, 8 (15124), ⟨10.1038/ncomms15124⟩. ⟨hal-01535806⟩