Saturday, 7 February 2015

Thioredoxin, the Ring Master of TCA Circus in Plant Mitochondria

Yes, we are talking about the tricarboxylic acid (TCA) cycle that is also known as Kreb's Cycle or citric acid cycle. You may be aware, this fundamental metabolic pathway is a sequence of enzymatic reactions in which the two carbon atoms of acetyl-CoA are oxidized to carbon dioxide. The overall reactions are complete oxidation of one molecule of acetyl-CoA, the production of two molecules of carbon dioxide, the reduction of of three molecules of NAD+ and one of FAD, and the phosphorylation of one molecule of GDP.

TCA cycle
There are four major regulatory enzymes in the citric acid cycle. 1. Citrate synthase catalyzes the condensation with oxaloacetate to produce citrate. 2. The conversion of isocitrate to 2-oxoglutarate, catalysed by isocitrate dehydrogenase. 3. The third regulatory enzyme is 2-oxoglutarate dehydrogenase.4. Succinate dehydrogenase  converts succinate to fumarate. Another important enzyme is fumarate hydratase (usually called fumarase) converts fumarate to malate.
The cycle enzyme-encoding genes also have been well characterized in terms of transcriptional and effector-mediated regulation and have also been subjected to reverse genetic analysis.

Then, what next? Next is, “What regulates flux through this pathway in vivo?”. Group of scientists (Danilo et.al,  2015) from Max Planck Institute of Molecular Plant Physiology, Germany  after demonstration of combination of experiments based on mutant and carbon isotope labeling analyses found that 'thioredoxin' (TRX) regulates the activity of enzymes of the mitochondrial cycle (succinate dehydrogenase and fumarase) and of an enzyme associated with it (ATP-citrate lyase) by modulating thiol redox status.
Thioredoxin
They first characterized, at the enzyme and metabolite levels, mutants of the mitochondrial TRX pathway in Arabidopsis: the NADP-TRX reductase a and b double mutant (ntra ntrb) and the mitochondrially located thioredoxin o1 (trxo1) mutant. These studies were followed by a comparative evaluation of the redistribution of isotopes when 13C-glucose, 13C-malate, or 13C-pyruvate was provided as a substrate to leaves of mutant or WT plants. In a complementary approach, they evaluated the in vitro activities of a range of TCA cycle and associated enzymes under varying redox states. The combined dataset suggests that TRX may deactivate both mitochondrial succinate dehydrogenase and fumarase and activate the cytosolic ATP-citrate lyase in vivo, acting as a direct regulator of carbon flow through the TCA cycle and providing a mechanism for the coordination of cellular function.

Reference
Danilo M. Daloso, Karolin Müller, Toshihiro Obata, Alexandra Florian, Takayuki Tohge, Alexandra Bottcher, Christophe Riondet, Laetitia Bariat, Fernando Carrari, Adriano Nunes-Nesi, Bob B. Buchanan, Jean-Philippe Reichheld, Wagner L. Araújo, and Alisdair R. Fernie. (2015) Thioredoxin, a master regulator of the tricarboxylic acid cycle in plant mitochondria. PNAS. published online on February 2, 2015, doi:10.1073/pnas.1424840112

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