scholarly journals A stalled-ribosome rescue factor Pth3 is required for mitochondrial translation against antibiotics in Saccharomyces cerevisiae

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Soichiro Hoshino ◽  
Ryohei Kanemura ◽  
Daisuke Kurita ◽  
Yukihiro Soutome ◽  
Hyouta Himeno ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Stop Codon ◽  
Mitochondrial Gene ◽  
Mrna Levels ◽  
Primary Role ◽  
Mitochondrial Gene Expression ◽  
Rt Pcr ◽  
Mitochondrial Translation ◽  
Mitochondrial Ribosomes ◽  
In Organello

AbstractMitochondrial translation appears to involve two stalled-ribosome rescue factors (srRFs). One srRF is an ICT1 protein from humans that rescues a “non-stop” type of mitochondrial ribosomes (mitoribosomes) stalled on mRNA lacking a stop codon, while the other, C12orf65, reportedly has functions that overlap with those of ICT1; however, its primary role remains unclear. We herein demonstrated that the Saccharomyces cerevisiae homolog of C12orf65, Pth3 (Rso55), preferentially rescued antibiotic-dependent stalled mitoribosomes, which appear to represent a “no-go” type of ribosomes stalled on intact mRNA. On media containing a non-fermentable carbon source, which requires mitochondrial gene expression, respiratory growth was impaired significantly more by the deletion of PTH3 than that of the ICT1 homolog PTH4 in the presence of antibiotics that inhibit mitochondrial translation, such as tetracyclines and macrolides. Additionally, the in organello labeling of mitochondrial translation products and quantification of mRNA levels by quantitative RT-PCR suggested that in the presence of tetracycline, the deletion of PTH3, but not PTH4, reduced the protein expression of all eight mtDNA-encoded genes at the post-transcriptional or translational level. These results indicate that Pth3 can function as a mitochondrial srRF specific for ribosomes stalled by antibiotics and plays a role in antibiotic resistance in fungi.

scholarly journals The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion and protein biogenesis in mitochondria

2018 ◽  
Vol 29 (20) ◽  
pp. 2386-2396 ◽  
Author(s):  
Braulio Vargas Möller-Hergt ◽  
Andreas Carlström ◽  
Katharina Stephan ◽  
Axel Imhof ◽  
Martin Ott
Keyword(s):  
Membrane Protein ◽  
Mitochondrial Gene ◽  
Ribosomal Subunit ◽  
Mitochondrial Translation ◽  
Protein Insertion ◽  
Mitochondrial Ribosomes ◽  
Protein Biogenesis ◽  
Membrane Bound ◽  
Highly Hydrophobic ◽  
Soluble C

Mitochondrial gene expression in Saccharomyces cerevisiae is responsible for the production of highly hydrophobic subunits of the oxidative phosphorylation system. Membrane insertion occurs cotranslationally on membrane-bound mitochondrial ribosomes. Here, by employing a systematic mass spectrometry–based approach, we discovered the previously uncharacterized membrane protein Mrx15 that interacts via a soluble C-terminal domain with the large ribosomal subunit. Mrx15 contacts mitochondrial translation products during their synthesis and plays, together with the ribosome receptor Mba1, an overlapping role in cotranslational protein insertion. Taken together, our data reveal how these ribosome receptors organize membrane protein biogenesis in mitochondria.

Regulation of mitochondrial gene expression in Saccharomyces cerevisiae: the role of RNA-binding enzymes

2001 ◽  
Vol 1 (S1) ◽  
Author(s):  
H van der Spek ◽  
M Siep ◽  
L de Jong ◽  
SDJ Elzinga ◽  
K van Oosterum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Rna Binding ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression

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

1988 ◽  
Vol 319 (1193) ◽  
pp. 97-105 ◽  
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.

scholarly journals Local translation in synaptic mitochondria influences synaptic transmission

2020 ◽  
Author(s):  
Roya Yousefi ◽  
Eugenio F. Fornasiero ◽  
Lukas Cyganek ◽  
Stefan Jakobs ◽  
Silvio O. Rizzoli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hippocampal Neurons ◽  
Spatial Organization ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Translation ◽  
Ample Evidence

ABSTRACTMitochondria possess a small genome that codes for core subunits of the oxidative phosphorylation system, and whose expression is essential for energy production. Information on the regulation and spatial organization of mitochondrial gene expression in the cellular context has been difficult to obtain. Here we addressed this by devising an imaging approach to analyze mitochondrial translation, by following the incorporation of clickable non-canonical amino acids. We applied this method to multiple cell types, including hippocampal neurons, where we found ample evidence for mitochondrial translation in both dendrites and axons. Translation levels were surprisingly heterogeneous, were typically stronger in axons, and were independent of their distance from the cell soma, where mitochondria presumably descent from. Presynaptic mitochondrial translation correlated with local synaptic activity, and blocking mitochondria translation reduced synaptic function. Overall, these findings demonstrate that mitochondrial gene expression in neurons is intimately linked to neuronal function.

scholarly journals Pet127p, a membrane-associated protein involved in stability and processing of Saccharomyces cerevisiae mitochondrial RNAs.

1997 ◽  
Vol 17 (5) ◽  
pp. 2816-2824 ◽  
Author(s):  
G Wiesenberger ◽  
T D Fox
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Processing ◽  
Mitochondrial Gene ◽  
Mitochondrial Gene Expression ◽  
Wild Type ◽  
Rna Surveillance ◽  
Nuclear Mutations ◽  
Membrane Bound ◽  
The Stability ◽  
Untranslated Leaders

Nuclear mutations that inactivate the Saccharomyces cerevisiae gene PET127 dramatically increased the levels of mutant COX3 and COX2 mitochondrial mRNAs that were destabilized by mutations in their 5' untranslated leaders. The stabilizing effect of pet127 delta mutations occurred both in the presence and in the absence of translation. In addition, pet127 delta mutations had pleiotropic effects on the stability and 5' end processing of some wild-type mRNAs and the 15S rRNA but produced only a leaky nonrespiratory phenotype at 37 degrees C. Overexpression of PET127 completely blocked respiratory growth and caused cells to lose wild-type mitochondrial DNA, suggesting that too much Pet127p prevents mitochondrial gene expression. Epitope-tagged Pet127p was specifically located in mitochondria and associated with membranes. These findings suggest that Pet127p plays a role in RNA surveillance and/or RNA processing and that these functions may be membrane bound in yeast mitochondria.

Coordination of nuclear and mitochondrial gene expression during the development of cardiac hypertrophy in rats

1994 ◽  
Vol 267 (1) ◽  
pp. C229-C235 ◽  
Author(s):  
R. J. Wiesner ◽  
V. Aschenbrenner ◽  
J. C. Ruegg ◽  
R. Zak
Keyword(s):  
Gene Expression ◽  
Cytochrome C ◽  
Cardiac Hypertrophy ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Gene ◽  
Nuclear Gene ◽  
Hormone Treatment ◽  
Mrna Levels ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Rrna

We studied the coordination of nuclear and mitochondrial gene expression during cardiac hypertrophy following aortic stenosis or thyroid hormone treatment in rats. We measured mRNA levels for representative subunits of cytochrome-c oxidase, two encoded by mitochondrial DNA and two encoded by the nucleus, as well as the levels of one mitochondrial rRNA. In both models of hypertrophy, an increase of total tissue RNA, reflecting mainly cytosolic ribosomes, accompanied the increase in ventricular weight. Relative levels of mitochondrial rRNA remained unchanged, indicating a net synthesis of mitochondrial ribosomes as well. In both models, cytochrome-c oxidase activity and nuclear-encoded mRNAs remained fairly constant, whereas levels of mitochondrial mRNAs were transiently decreased 24 h after the growth stimulus. We conclude that, in the initial phase of hypertrophy, the signal regulating the synthesis of mitochondrial rRNA is synchronized with nuclear gene expression, whereas the signal regulating mitochondrial mRNA synthesis is not. We postulate that differential regulation of mitochondrial transcription and premature termination of the polycistronic transcript (the latter giving rise to the mitochondrial rRNAs) account for the observed results.

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