[PDF][PDF] A single adaptable cochaperone-scaffold complex delivers nascent iron-sulfur clusters to mammalian respiratory chain complexes I–III

N Maio, KS Kim, A Singh, TA Rouault - Cell metabolism, 2017 - cell.com
N Maio, KS Kim, A Singh, TA Rouault
Cell metabolism, 2017cell.com
The iron-sulfur (Fe-S) cluster of the Rieske protein, UQCRFS1, is essential for Complex III
(CIII) activity, though the mechanism for Fe-S cluster transfer has not previously been
elucidated. Recent studies have shown that the co-chaperone HSC20, essential for Fe-S
cluster biogenesis of SDHB, directly binds LYRM7, formerly described as a chaperone that
stabilizes UQCRFS1 prior to its insertion into CIII. Here we report that a transient
subcomplex involved in CIII assembly, composed of LYRM7 bound to UQCRFS1, interacts …
Summary
The iron-sulfur (Fe-S) cluster of the Rieske protein, UQCRFS1, is essential for Complex III (CIII) activity, though the mechanism for Fe-S cluster transfer has not previously been elucidated. Recent studies have shown that the co-chaperone HSC20, essential for Fe-S cluster biogenesis of SDHB, directly binds LYRM7, formerly described as a chaperone that stabilizes UQCRFS1 prior to its insertion into CIII. Here we report that a transient subcomplex involved in CIII assembly, composed of LYRM7 bound to UQCRFS1, interacts with components of an Fe-S transfer complex, consisting of HSC20, its cognate chaperone HSPA9, and the holo-scaffold ISCU. Binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates Fe-S cluster transfer to UQCRFS1. The five Fe-S cluster subunits of Complex I also interact with HSC20 to acquire their clusters, highlighting the crucial role of HSC20 in the assembly of the mitochondrial respiratory chain.
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