Mitochondrial Metabolism in the Spotlight: Maintaining Balanced RNAP III Activity Ensures Cellular Homeostasis
Abstract
:1. Introduction
2. Results
2.1. 13C Flux through the TCA Cycle Is Affected Indirectly by RNAP III Activity on Glucose
2.2. Lower Flux toward Glutamate in the MAF1-Deficient Mutant Can Be Compensated by Its Suppressor’s High Metabolic Activity in Glutamate Synthesis
2.3. Elevated Temperature along with Non-Fermentative Glycerol Further Abolishes TCA Cycle Activity in maf1∆
2.4. Malic Enzyme Is the Key Enzyme Responsible for Cataplerosis in maf1∆ Affecting the Mutant Viability
2.5. Reductive Carboxylation of Glutamine Is the Survival Strategy of rpc128-1007 Grown on Glucose
2.6. maf1∆ and rpc128-1007 Show Enhanced acetyl-CoA and Lipids Content
3. Discussion
3.1. RNAP III Non-Optimal Activity Affects the TCA Flux and TCA Enzymes Activities
3.2. The Difference in Growth of the Mutants with Altered RNAP III Activity on a Non-Fermentable Carbon Source Results from Flux Rerouting
4. Materials and Methods
4.1. Yeast Culturing and Metabolites Extraction for 13C Flux Analysis by Nuclear Magnetic Resonance (NMR) Spectroscopy
4.2. NMR Spectroscopy
4.3. Metabolism Modelling
4.4. NADH-Linked Enzymatic Assays
4.5. Acetyl-CoA, NAD+ and NADH Measurement
4.6. Lipid Extraction and Staining
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Szatkowska, R.; Furmanek, E.; Kierzek, A.M.; Ludwig, C.; Adamczyk, M. Mitochondrial Metabolism in the Spotlight: Maintaining Balanced RNAP III Activity Ensures Cellular Homeostasis. Int. J. Mol. Sci. 2023, 24, 14763. https://doi.org/10.3390/ijms241914763
Szatkowska R, Furmanek E, Kierzek AM, Ludwig C, Adamczyk M. Mitochondrial Metabolism in the Spotlight: Maintaining Balanced RNAP III Activity Ensures Cellular Homeostasis. International Journal of Molecular Sciences. 2023; 24(19):14763. https://doi.org/10.3390/ijms241914763
Chicago/Turabian StyleSzatkowska, Roza, Emil Furmanek, Andrzej M. Kierzek, Christian Ludwig, and Malgorzata Adamczyk. 2023. "Mitochondrial Metabolism in the Spotlight: Maintaining Balanced RNAP III Activity Ensures Cellular Homeostasis" International Journal of Molecular Sciences 24, no. 19: 14763. https://doi.org/10.3390/ijms241914763