Mitochondrial Bol1 and Bol3 Function As Assembly Factors for Specific Iron-sulfur Proteins

Overview

Journal Elife

Specialty Biology

Date 2016 Aug 18

PMID 27532772

Citations 59

Authors

Marta A Uzarska

Veronica Nasta

Benjamin D Weiler

Farah Spantgar

Simone Ciofi-Baffoni

Maria Rosaria Saviello

Leonardo Gonnelli

Ulrich Muhlenhoff

Lucia Banci

Roland Lill

Affiliations

Soon will be listed here.

Abstract

Assembly of mitochondrial iron-sulfur (Fe/S) proteins is a key process of cells, and defects cause many rare diseases. In the first phase of this pathway, ten Fe/S cluster (ISC) assembly components synthesize and insert [2Fe-2S] clusters. The second phase is dedicated to the assembly of [4Fe-4S] proteins, yet this part is poorly understood. Here, we characterize the BOLA family proteins Bol1 and Bol3 as specific mitochondrial ISC assembly factors that facilitate [4Fe-4S] cluster insertion into a subset of mitochondrial proteins such as lipoate synthase and succinate dehydrogenase. Bol1-Bol3 perform largely overlapping functions, yet cannot replace the ISC protein Nfu1 that also participates in this phase of Fe/S protein biogenesis. Bol1 and Bol3 form dimeric complexes with both monothiol glutaredoxin Grx5 and Nfu1. Complex formation differentially influences the stability of the Grx5-Bol-shared Fe/S clusters. Our findings provide the biochemical basis for explaining the pathological phenotypes of patients with mutations in BOLA3.

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