A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I–III

Publication date: 4 April 2017
Source:Cell Metabolism, Volume 25, Issue 4
Author(s): Nunziata Maio, Ki Soon Kim, Anamika Singh, Tracey A. Rouault
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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Teaser

Maio et al. identify the crucial role of the co-chaperone HSC20 for the assembly and function of the mitochondrial respiratory chain. Their work also highlights that Complexes I–III share a common molecular mechanism for Fe-S cluster acquisition.


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