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

verfasst von

Anna Moseler, Inga Kruse, Andrew E Maclean, Luca Pedroletti, Marina Franceschetti, Stephan Wagner, Regina Wehler, Katrin Fischer-Schrader, Gernot Poschet, Markus Wirtz, Peter Dörmann, Tatjana M Hildebrandt, Rüdiger Hell, Markus Schwarzländer, Janneke Balk, Andreas J Meyer

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.

Organisationseinheit(en)

Institut für Pflanzengenetik

Externe Organisation(en)

Rheinische Friedrich-Wilhelms-Universität Bonn
Universität zu Köln
Ruprecht-Karls-Universität Heidelberg
Westfälische Wilhelms-Universität Münster (WWU)
Université de Lorraine (UL)
University of East Anglia
John Innes Centre
Forschungszentrum Jülich

Typ

Artikel

Journal

Plant physiology

Band

186

Seiten

1507-1525

Anzahl der Seiten

19

ISSN

0032-0889

Publikationsdatum

07.2021

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Genetik, Physiologie, Pflanzenkunde

Elektronische Version(en)

https://doi.org/10.1093/plphys/kiab172 (Zugang: Offen)