ISCA1 is essential for mitochondrial Fe4S4 biogenesis in vivo

Lena Kristina Beilschmidt, Sandrine Ollagnier de Choudens, Marjorie Fournier, Ioannis Sanakis, Marc-André Hograindleur, Martin Clémancey, Geneviève Blondin, Stéphane Schmucker, Aurélie Eisenmann, Amélie Weiss, Pascale Koebel, Nadia Messaddeq, Hélène Puccio () and Alain Martelli ()
Additional contact information
Lena Kristina Beilschmidt: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Sandrine Ollagnier de Choudens: CEA/DRF/BIG/CBM/BioCat
Marjorie Fournier: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Ioannis Sanakis: NCSR, Demokritos, Institut of Materials Science
Marc-André Hograindleur: CEA/DRF/BIG/CBM/BioCat
Martin Clémancey: CNRS UMR 5249, LCBM
Geneviève Blondin: CNRS UMR 5249, LCBM
Stéphane Schmucker: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Aurélie Eisenmann: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Amélie Weiss: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Pascale Koebel: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Nadia Messaddeq: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Hélène Puccio: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department
Alain Martelli: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Translational Medicine and Neurogenetics Department

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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 Fe4S4 proteins biogenesis. Collectively, our data suggest that cellular processes with different requirements for ISCA1, ISCA2 and ISCA1–ISCA2 complex seem to exist.

Date: 2017
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DOI: 10.1038/ncomms15124

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