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Nat Commun. 2017 May 11;8:15124. doi: 10.1038/ncomms15124.

ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo.

Beilschmidt LK1,2,3,4,5, Ollagnier de Choudens S6,7,8, Fournier M1,2,3,4, Sanakis I9, Hograindleur MA6,7,8,10, Clémancey M7,8,10, Blondin G7,8,10, Schmucker S1,2,3,4,5, Eisenmann A1,2,3,4,5, Weiss A1,2,3,4, Koebel P1,2,3,4, Messaddeq N1,2,3,4, Puccio H1,2,3,4,5, Martelli A1,2,3,4,5.

Author information

IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department, 67404 Illkirch, France.
Inserm U596, 67404 Illkirch, France.
CNRS, UMR7104, 67404 Illkirch, France.
Université de Strasbourg, 67000 Strasbourg, France.
Collège de France, Chaire de Génétique Humaine, 67404 Illkirch, France.
CEA/DRF/BIG/CBM/BioCat, 38054 Grenoble, France.
CNRS UMR 5249, LCBM, 38054 Grenoble, France.
Université Grenoble Alpes, LCBM, 38054 Grenoble, France.
NCSR, Demokritos, Institut of Materials Science, Attiki, Greece.
CEA/DRF/BIG/CBM/pmb, 38054 Grenoble, France.


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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