scholarly journals Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in Mitochondrial Gene Expression

2021 ◽  
Vol 22 (5) ◽  
pp. 2746
Author(s):  
Dimitri Shcherbakov ◽  
Reda Juskeviciene ◽  
Adrián Cortés Sanchón ◽  
Margarita Brilkova ◽  
Hubert Rehrauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Response ◽  
Mitochondrial Gene ◽  
Tca Cycle ◽  
Brain Mitochondria ◽  
Mitochondrial Gene Expression ◽  
Rna Seq ◽  
The Tca Cycle ◽  
Neurological Phenotype

Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, in-vivo is associated with a subtle neurological phenotype. Brain mitochondria of homozygous knock-in mutant Mrps5V338Y/V338Y mice show decreased oxygen consumption and reduced ATP levels. Using a combination of unbiased RNA-Seq with untargeted metabolomics, we here demonstrate a concerted response, which alleviates the impaired functionality of OXPHOS complexes in Mrps5 mutant mice. This concerted response mitigates the age-associated decline in mitochondrial gene expression and compensates for impaired respiration by transcriptional upregulation of OXPHOS components together with anaplerotic replenishment of the TCA cycle (pyruvate, 2-ketoglutarate).

Metabolic factors in the development of hepatic steatosis and altered mitochondrial gene expression in vivo

Metabolism ◽  
2011 ◽  
Vol 60 (8) ◽  
pp. 1090-1099 ◽  
Author(s):  
Shaoyun Wang ◽  
Amrita Kamat ◽  
Pablo Pergola ◽  
Anita Swamy ◽  
Fermin Tio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatic Steatosis ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression ◽  
Metabolic Factors

Mitochondrial gene expression in the human annulus: in vivo data from annulus cells and selectively harvested senescent annulus cells

2011 ◽  
Vol 11 (8) ◽  
pp. 782-791 ◽  
Author(s):  
Helen E. Gruber ◽  
John A. Watts ◽  
Gretchen L. Hoelscher ◽  
Synthia F. Bethea ◽  
Jane A. Ingram ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression

scholarly journals In-Depth Profiling of Lysine-Producing Corynebacterium glutamicum by Combined Analysis of the Transcriptome, Metabolome, and Fluxome

2004 ◽  
Vol 186 (6) ◽  
pp. 1769-1784 ◽  
Author(s):  
Jens Olaf Krömer ◽  
Oliver Sorgenfrei ◽  
Kai Klopprogge ◽  
Elmar Heinzle ◽  
Christoph Wittmann
Keyword(s):  
Gene Expression ◽  
Glucose Uptake ◽  
Corynebacterium Glutamicum ◽  
Tca Cycle ◽  
Lysine Biosynthesis ◽  
Intracellular Metabolite ◽  
Lysine Production ◽  
The Tca Cycle ◽  
Depth Analysis

ABSTRACT An in-depth analysis of the intracellular metabolite concentrations, metabolic fluxes, and gene expression (metabolome, fluxome, and transcriptome, respectively) of lysine-producing Corynebacterium glutamicum ATCC 13287 was performed at different stages of batch culture and revealed distinct phases of growth and lysine production. For this purpose, 13C flux analysis with gas chromatography-mass spectrometry-labeling measurement of free intracellular amino acids, metabolite balancing, and isotopomer modeling were combined with expression profiling via DNA microarrays and with intracellular metabolite quantification. The phase shift from growth to lysine production was accompanied by a decrease in glucose uptake flux, the redirection of flux from the tricarboxylic acid (TCA) cycle towards anaplerotic carboxylation and lysine biosynthesis, transient dynamics of intracellular metabolite pools, such as an increase of lysine up to 40 mM prior to its excretion, and complex changes in the expression of genes for central metabolism. The integrated approach was valuable for the identification of correlations between gene expression and in vivo activity for numerous enzymes. The glucose uptake flux closely corresponded to the expression of glucose phosphotransferase genes. A correlation between flux and expression was also observed for glucose-6-phosphate dehydrogenase, transaldolase, and transketolase and for most TCA cycle genes. In contrast, cytoplasmic malate dehydrogenase expression increased despite a reduction of the TCA cycle flux, probably related to its contribution to NADH regeneration under conditions of reduced growth. Most genes for lysine biosynthesis showed a constant expression level, despite a marked change of the metabolic flux, indicating that they are strongly regulated at the metabolic level. Glyoxylate cycle genes were continuously expressed, but the pathway exhibited in vivo activity only in the later stage. The most pronounced changes in gene expression during cultivation were found for enzymes at entry points into glycolysis, the pentose phosphate pathway, the TCA cycle, and lysine biosynthesis, indicating that these might be of special importance for transcriptional control in C. glutamicum.

Abstract P443: Loss Of Pkm2 Alters Myocardial Metabolism And Increases Oxidative Stress After Infarction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Katie C Lee ◽  
Allison L Williams ◽  
Ralph V Shohet
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Tca Cycle ◽  
Pentose Phosphate ◽  
Mitochondrial Enzymes ◽  
Rna Seq ◽  
Atp Production ◽  
The Tca Cycle ◽  
Alternatively Spliced ◽  
Altered Gene

Introduction: Pyruvate kinase (Pkm1) directs pyruvate to the TCA cycle for oxidative metabolism in the healthy heart. Our lab described a hypoxia-mediated switch to the alternatively spliced isoform Pkm2, enhancing pyruvate to lactate conversion. Recently, we have also found that Pkm2 knockout (KO) mice had profound depletion of basal glucose in the heart compared to control mice. Pkm2 has also been shown to reduce oxidative damage and promote cardiomyocyte cell proliferation after myocardial infarction (MI). We hypothesize that the upregulation of Pkm2 alters metabolic pathways after injury to promote glycolysis and preserve ATP production in hypoxia, which protects the heart from the stresses of hypoxia and injury. Methods: Global Pkm2 KO mice were subjected to permanent ligation of the left anterior descending coronary artery to mimic an MI. RNA-seq analysis of left ventricles from control (n=8) and Pkm2 KO mice (n=8) before and 3 days after sham or MI surgery was performed. Semiquantitative real-time PCR (qPCR) was used to confirm changes in selected genes of interest. Results: Loss of Pkm2 did not alter gene expression substantially at baseline. 68 genes were differentially expressed in Pkm2 KO hearts after MI (q<0.05, FDR<0.05) not observed in control MI hearts. MI in Pkm2 KO hearts resulted in considerable reduction of transcripts of enzymes in the insulin signaling pathway, mitochondrial oxidative phosphorylation, fatty acid metabolism, and increase in transcripts encoding enzymes in the pentose phosphate pathway, response to oxidative stress, and apoptotic signaling. qPCR of selected genes involved in glucose metabolism confirmed RNA-seq results. Conclusions: RNA-seq analysis of Pkm2 KO hearts demonstrated that loss of Pkm2 altered gene expression of metabolic and mitochondrial enzymes. Conversely, Pkm2 KO hearts showed increased abundance of pro-apoptotic markers which may be a result of increased oxidative stress.

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

scholarly journals Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle.

1986 ◽  
Vol 261 (1) ◽  
pp. 376-380 ◽  
Author(s):  
R S Williams ◽  
S Salmons ◽  
E A Newsholme ◽  
R E Kaufman ◽  
J Mellor
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Contractile Activity ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression
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