Genetic evidence that different functional domains of the PET54 gene product facilitate expression of the mitochondrial genes COX1 and COX3 in Saccharomyces cerevisiae.

Expression of the yeast mitochondrial genes COX1 and COX3, which encode subunits I and III of cytochrome oxidase, respectively, is controlled by a common nuclear-encoded trans-acting factor. This protein, encoded by the PET54 gene, controls expression of COX1 at the level of RNA splicing and COX3 at the level of mRNA translation. While the steps of COX1 and COX3 gene expression affected by the PET54 gene product are different, it is possible that the PET54 protein is monofunctional and affects expression of each gene by a single mechanism, such as modulation of RNA secondary structure. The goal of this study was to address whether the PET54 protein is monofunctional or multifunctional with respect to its role in COX1 and COX3 gene expression. Ten insertion mutations, which each resulted in the in-frame addition of four amino acids within the PET54 polypeptide, were generated, and the resulting mutants were characterized for respiration phenotype and mitochondrial gene expression. Five of the ten mutants were respiration deficient. Two of these five mutants were defective in expression of COX3 but not in expression of COX1, while two other mutants had the opposite phenotype (primarily defective in expression of COX1). The fifth mutant was equally defective in expression of both genes. These results demonstrate that the two functions of PET54 are genetically separable and support the idea that the PET54 protein is multifunctional.

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Translational regulation of mitochondrial gene expression by nuclear genes of Saccharomyces cerevisiae

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1988.0034 ◽

1988 ◽

Vol 319 (1193) ◽

pp. 97-105 ◽

Cited By ~ 22

Keyword(s):

Gene Expression ◽

Mitochondrial Gene ◽

Nuclear Gene ◽

Mitochondrial Genes ◽

Nuclear Genes ◽

Mitochondrial Gene Expression ◽

Wild Type ◽

Mitochondrial Translation ◽

Coding Sequence ◽

Sites Of Action

We describe several yeast nuclear mutations that specifically block expression of the mitochondrial genes encoding cytochrome c oxidase subunits II (COXII) and III (COXIII). These recessive mutations define positive regulators of mitochondrial gene expression that act at the level of translation. Mutations in the nuclear gene PET111 completely block accumulation of COXII, but the COXII mRNA is present in mutant cells at a level approximately one-third of that of the wild type. Mitochondrial suppressors of pet 111 mutations correspond to deletions in mtDNA that result in fusions between the cox II structural gene and other mitochondrial genes. The chimeric mRNAs encoded by these fusions are translated in pet 111 mutants; this translation leads to accumulation of functional COXII. The PET111 protein probably acts directly on cox II translation, because it is located in mitochondria. Translation of the mitochondrially coded mRNA for COXIII requires the action of at least three nuclear genes, PET 494, and a newly discovered gene, provisionally termed PET 55. Both the PET494 and PET54 proteins are located in mitochondria and therefore probably act directly on the mitochondrial translation system. Mutations in all three genes are suppressed in strains that contain chimeric cox III mRNAs with the 5'-untranslated leaders of other mitochondrial transcripts fused to the cox III coding sequence. The products of all three nuclear genes may form a complex and carry out a single function. A direct demonstration that the wild-type nuclear gene products act in the cox III 5'-leader has been obtained by showing that they are all required for translation of apocytochrome b from a novel mRNA consisting of the cox lIl 5'-leader attached to the cytochrome b coding sequence. The site (or sites) of action maps at least 172 bases upstream from the cox lll initiation codon in the 600 base cox III leader. Others have reported evidence which suggests that cox Ill translation is repressed by glucose. Consistently with the possibility that the nuclear genes described here may play a role in modulating mitochondrial gene expression, we have found that PET 494 expression is glucose-repressed.

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Faculty Opinions recommendation of Adult-onset obesity is triggered by impaired mitochondrial gene expression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.728768996.793536505 ◽

2017 ◽

Author(s):

Michael Miller ◽

Ekta Tiwary

Keyword(s):

Gene Expression ◽

Mitochondrial Gene ◽

Mitochondrial Gene Expression ◽

Adult Onset

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Neuroprotection by Progesterone through Stimulation of Mitochondrial Gene Expression

10.21236/ada392823 ◽

2000 ◽

Author(s):

Gary Fiskum

Keyword(s):

Gene Expression ◽

Mitochondrial Gene ◽

Mitochondrial Gene Expression ◽

Stimulation Of

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Mitochondrial Glucocorticoid Receptors and Their Actions

International Journal of Molecular Sciences ◽

10.3390/ijms22116054 ◽

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22052746 ◽

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).

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

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)42482-3 ◽

1986 ◽

Vol 261 (1) ◽

pp. 376-380 ◽

Cited By ~ 15

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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Quantitative proteomics revealed C6orf203/MTRES1 as a factor preventing stress-induced transcription deficiency in human mitochondria

Nucleic Acids Research ◽

10.1093/nar/gkz542 ◽

2019 ◽

Vol 47 (14) ◽

pp. 7502-7517 ◽

Cited By ~ 6

Author(s):

Anna V Kotrys ◽

Dominik Cysewski ◽

Sylwia D Czarnomska ◽

Zbigniew Pietras ◽

Lukasz S Borowski ◽

...

Keyword(s):

Gene Expression ◽

Rna Binding ◽

Mitochondrial Gene ◽

Binding Activity ◽

Stress Conditions ◽

Mitochondrial Rna ◽

Mitochondrial Gene Expression ◽

Compensatory Mechanisms ◽

Temporary Reduction ◽

Mitochondrial Transcription

AbstractMaintenance of mitochondrial gene expression is crucial for cellular homeostasis. Stress conditions may lead to a temporary reduction of mitochondrial genome copy number, raising the risk of insufficient expression of mitochondrial encoded genes. Little is known how compensatory mechanisms operate to maintain proper mitochondrial transcripts levels upon disturbed transcription and which proteins are involved in them. Here we performed a quantitative proteomic screen to search for proteins that sustain expression of mtDNA under stress conditions. Analysis of stress-induced changes of the human mitochondrial proteome led to the identification of several proteins with poorly defined functions among which we focused on C6orf203, which we named MTRES1 (Mitochondrial Transcription Rescue Factor 1). We found that the level of MTRES1 is elevated in cells under stress and we show that this upregulation of MTRES1 prevents mitochondrial transcript loss under perturbed mitochondrial gene expression. This protective effect depends on the RNA binding activity of MTRES1. Functional analysis revealed that MTRES1 associates with mitochondrial RNA polymerase POLRMT and acts by increasing mitochondrial transcription, without changing the stability of mitochondrial RNAs. We propose that MTRES1 is an example of a protein that protects the cell from mitochondrial RNA loss during stress.

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