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Aim32p is a Novel Member of the Erv1 Translocation Pathway within the Mitochondrial Intermembrane Space of Saccharomyces cerevisiae
Author(s) -
Dabir Deepa Vinay,
Nguyen Kevin,
Koehler Carla
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.600.14
Subject(s) - intermembrane space , oxidative folding , ferredoxin , mitochondrial intermembrane space , biochemistry , biology , microbiology and biotechnology , mitochondrial membrane transport protein , saccharomyces cerevisiae , mitochondrion , thioredoxin , cytosol , chemistry , yeast , protein disulfide isomerase , inner mitochondrial membrane , oxidative stress , gene , endoplasmic reticulum , bacterial outer membrane , escherichia coli , enzyme
The mitochondrion is a key player in basic cellular homeostasis in eukaryotic cells, contributing to the synthesis of ATP, prevention of oxidative damage from reactive oxygen species and regulation of cell death. In yeast, most mitochondrial proteins are synthesized in the cytoplasm and imported post‐translationally into the organelle. One particularly interesting translocation pathway is the Erv1 oxidative folding pathway, a disulfide relay system comprising of Erv1 and Mia40 that couples the folding, oxidation and import of proteins into the mitochondrial intermembrane space (IMS). Besides import of proteins, Erv1 has diverse functions in the IMS; these include reoxidation of Mia40 upon release of the client protein, maturation of cytosolic iron‐sulfur cluster‐containing proteins and in the biogenesis of the TIM22 translocation pathway. Considering that Erv1 has several key functions in the IMS, we hypothesized that additional Erv1 partner proteins exist that function as electron acceptors and/or substrates. In this study, we elucidate the biological functions of Aim32p; a newly identified Erv1‐binding protein. Aim32p is an IMS‐ resident and under native conditions co‐exists in a complex with Erv1 and Osm1. Osm1 is a fumarate reducatase and has been recently postulated to function as an anaerobic electron acceptor of Erv1. Our structure predictions based on sequence analysis and homology modeling suggest that Aim32p is a putative thioredoxin‐ like ferredoxin protein. Although the function of most thioredoxin‐like ferredoxins remains unknown, the presence of a putative thioredoxin fold and a ferredoxin domain in Aim32p is highly suggestive of a role in redox sensing and electron transfer. Interestingly, loss of Aim32p also confers severe sensitivity to DNA damaging agents, MMS (Methyl methanesulfonate) and Hydroxyurea (HU). Thus, Aim32p may have a dual role in the mitochondrial IMS, participating in electron transfer reactions with Erv1 singularly or as a redox couple along with Osm1, and function in DNA damage stress response. Importantly, this study connects the redox‐regulated Erv1 translocation pathway to DNA damage stress response, and consequently its importance and versatility in several fundamental processes of the mitochondria. Support or Funding Information This work is supported by the Kadner Pitts grant.