Thioredoxins o1 and h2 jointly adjust mitochondrial dihydrolipoamide dehydrogenase‐dependent pathways towards changing environments

• Published in: Plant, cell and environment cell and environment, 2024-07, Vol.47 (7), p.2542-2560
• Main Authors: Timm, Stefan, Klaas, Nicole, Niemann, Janice, Jahnke, Kathrin, Alseekh, Saleh, Zhang, Youjun, Souza, Paulo V. L., Hou, Liang‐Yu, Cosse, Maike, Selinski, Jennifer, Geigenberger, Peter, Daloso, Danilo M., Fernie, Alisdair R., Hagemann, Martin
• Format: Article
• Language: English
• Subjects: Amino acids; Arabidopsis; Arabidopsis - enzymology; Arabidopsis - genetics; Arabidopsis - metabolism; Biochemical analysis; Biodegradation; Carbon dioxide; Carbon Dioxide - metabolism; Chain branching; Changing environments; Dehydrogenase; Dehydrogenases; Dihydrolipoamide Dehydrogenase - genetics; Dihydrolipoamide Dehydrogenase - metabolism; Environment; environmental acclimation; Environmental changes; Environmental conditions; Environmental degradation; Enzymatic activity; Glycine; Labeling; metabolic regulation; Metabolism; Metabolites; Mitochondria; Mitochondria - metabolism; Mutation; NAD - metabolism; Nicotinamide adenine dinucleotide; Nucleotides; Oxidation-Reduction; Phenotypes; Photorespiration; Photosynthesis; Plant Proteins - genetics; Plant Proteins - metabolism; Pyridine nucleotides; Redox properties; redox regulation; Thioredoxins - metabolism; Tricarboxylic acid cycle
• ISSN: 0140-7791; 1365-3040; 1365-3040
• DOI: 10.1111/pce.14899

Thioredoxins (TRXs) are central to redox regulation, modulating enzyme activities to adapt metabolism to environmental changes. Previous research emphasized mitochondrial and microsomal TRX o1 and h2 influence on mitochondrial metabolism, including photorespiration and the tricarboxylic acid (TCA) cycle. Our study aimed to compare TRX‐based regulation circuits towards environmental cues mainly affecting photorespiration. Metabolite snapshots, phenotypes and CO2 assimilation were compared among single and multiple TRX mutants in the wild‐type and the glycine decarboxylase T‐protein knockdown (gldt1) background. Our analyses provided evidence for additive negative effects of combined TRX o1 and h2 deficiency on growth and photosynthesis. Especially metabolite accumulation patterns suggest a shared regulation mechanism mainly on mitochondrial dihydrolipoamide dehydrogenase (mtLPD1)‐dependent pathways. Quantification of pyridine nucleotides, in conjunction with 13C‐labelling approaches, and biochemical analysis of recombinant mtLPD1 supported this. It also revealed mtLPD1 inhibition by NADH, pointing at an additional measure to fine‐tune it's activity. Collectively, we propose that lack of TRX o1 and h2 perturbs the mitochondrial redox state, which impacts on other pathways through shifts in the NADH/NAD+ ratio via mtLPD1. This regulation module might represent a node for simultaneous adjustments of photorespiration, the TCA cycle and branched chain amino acid degradation under fluctuating environmental conditions. Summary statement Thioredoxins o1 and h2 concertedly adapt the performance of mtLPD1‐dependent pathways towards short‐ and long‐term environmental changes. Simultaneous adjustments of mitochondrial pathway fluxes are achieved through fine tuning of mtLPD1 activity via redox regulation and subcellular NADH/NAD+ ratios.