Molecular chaperones involved in mitochondrial iron-sulfur protein biogenesis

Rafał Dutkiewicz , Agnieszka Nowak

Abstract

Iron-sulfur (FeS) clusters are prosthetic groups critical for the function of many proteins in all domains of life. FeS proteins function in processes ranging from oxidative phosphorylation and cofactor biosyntheses to DNA/RNA metabolism and regulation of gene expression. In eukaryotic cells, mitochondria play a central role in the process of FeS biogenesis and support maturation of FeS proteins localized within mitochondria and in other cellular compartments. In humans, defects in mitochondrial FeS cluster biogenesis lead to numerous pathologies, which are often fatal. The generation of FeS clusters in mitochondria is a complex process. The [2Fe–2S] cluster is first assembled on a dedicated scaffold protein (Isu1) by the action of protein factors that interact with Isu1 to form the “assembly complex”. Next, the FeS cluster is transferred onto a recipient apo-protein. Genetic and biochemical evidence implicates participation of a specialized J-protein co-chaperone Jac1 and its mitochondrial (mt)Hsp70 chaperone partner, and the glutaredoxin Grx5 in the FeS cluster transfer process. Finally, various specialized ISC components assist in the generation of [4Fe-4S] clusters and cluster insertion into specific target apoproteins. Although a framework of protein components that are involved in the mitochondrial FeS cluster biogenesis has been established based on genetic and biochemical studies, detailed molecular mechanisms involved in this important and medically relevant process are not well understood. This review summarizes our molecular knowledge on chaperone proteins’ functions during the FeS protein biogenesis.
Author Rafał Dutkiewicz KBMiK
Rafał Dutkiewicz,,
- Department of Molecular and Cellular Biology
, Agnieszka Nowak MWB UG i GUMed
Agnieszka Nowak,,
- Intercollegiate Faculty of Biotechnology UG
Journal seriesJournal of Biological Inorganic Chemistry, ISSN 0949-8257
Issue year2018
Vol23
No4
Pages569-579
Publication size in sheets0.5
Keywords in EnglishJ-domain proteins, Hsp70, iron-sulfur clusters, mitochondria, yeast
DOIDOI:10.1007/s00775-017-1504-x
URL https://link.springer.com/content/pdf/10.1007%2Fs00775-017-1504-x.pdf
Languageen angielski
LicenseOther; published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)35
ScoreMinisterial score = 30.0, 21-06-2018, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 21-06-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 2.894 (2) - 2016=2.681 (5)
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