The function of glutaredoxin GRXS15 is required for lipoyl-dependent dehydrogenases in mitochondria

Moseler, A. et al. (2021) The function of glutaredoxin GRXS15 is required for lipoyl-dependent dehydrogenases in mitochondria. Plant Physiology, 186(3), pp. 1507-1525. (doi: 10.1093/plphys/kiab172) (PMID:33856472)

Abstract

Iron-sulfur (Fe-S) clusters are ubiquitous cofactors in all life and are used in a wide array of diverse biological processes, including electron transfer chains and several metabolic pathways. Biosynthesis machineries for Fe-S clusters exist in plastids, the cytosol and mitochondria. A single monothiol glutaredoxin (GRX) is involved in Fe-S cluster assembly in mitochondria of yeast and mammals. In plants, the role of the mitochondrial homologue GRXS15 has only partially been characterized. Arabidopsis (Arabidopsis thaliana) grxs15 null mutants are not viable, but mutants complemented with the variant GRXS15 K83A develop with a dwarf phenotype similar to the knockdown line GRXS15amiR. In an in-depth metabolic analysis of the variant and knockdown GRXS15 lines, we show that most Fe-S cluster-dependent processes are not affected, including biotin biosynthesis, molybdenum cofactor biosynthesis, the electron transport chain and aconitase in the TCA cycle. Instead, we observed an increase in most TCA cycle intermediates and amino acids, especially pyruvate, glycine and branched-chain amino acids (BCAAs). Additionally, we found an accumulation of branched-chain α-keto acids (BCKAs), the first degradation products resulting from transamination of BCAAs. In wild-type plants, pyruvate, glycine and BCKAs are all metabolized through decarboxylation by mitochondrial lipoyl cofactor-dependent dehydrogenase complexes. These enzyme complexes are very abundant, comprising a major sink for lipoyl cofactor. Because biosynthesis of lipoyl cofactor depends on continuous Fe-S cluster supply to lipoyl synthase, this could explain why lipoyl cofactor-dependent processes are most sensitive to restricted Fe-S supply in grxs15 mutants.

• Item Type: Articles
• Additional Information: This work was supported by grants of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) through the priority program SPP1710 ‘Dynamics of thiolbased redox switches in cellular physiology’ (ME1567/9-1/2, SCHW1719/7-1, HE1848/16-1), the Emmy Noether programme (SCHW1719/1-1), an individual grant (ME1567/13-1), and through the Research Training Group 2064 ‘Water use efficiency and drought stress responses: From Arabidopsis to Barley’. I.K. was funded by the Doctoral Training Programme of the Biotechnology and Biological Sciences Research Council (BBSRC); A.E.M. was funded by a PhD studentship from the John Innes Foundation; M. F. and J.B. are funded by BBSRC grant awards BB/P012523/1 and BB/P012574/1. A.M. is recipient of a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacLean, Dr Andrew
• Authors: Moseler, A., Kruse, I., Maclean, A. E., Pedroletti, L., Franceschetti, M., Wagner, S., Wehler, R., Fischer-Schrader, K., Poschet, G., Wirtz, M., Dörmann, P., Hildebrandt, T. M., Hell, R., Schwarzländer, M., Balk, J., and Meyer, A. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Plant Physiology
• Publisher: American Society of Plant Biologists
• ISSN: 0032-0889
• ISSN (Online): 1532-2548
• Published Online: 15 April 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Plant Physiology 186(3): 1507-1525
• Publisher Policy: Reproduced under a Creative Commons License