Decreased total ventricular and mitochondrial protein synthesis during extended anoxia in turtle heart

1996 ◽  
Vol 271 (6) ◽  
pp. R1660-R1667 ◽  
Author(s):  
J. R. Bailey ◽  
W. R. Driedzic
Keyword(s):  
Protein Synthesis ◽  
Energy Levels ◽  
Mitochondrial Protein ◽  
Atp Synthesis ◽  
Cellular Protein ◽  
Control Mechanisms ◽  
Mitochondrial Protein Synthesis ◽  
Available Energy ◽  
Pressure Development ◽  
Turtle Heart

The turtle heart provides a model system to study the effects of anoxia on protein synthesis without the potentially confounding factor of contractile failure and decreased ATP levels. Protein synthesis, as measured by 3H-labeled phenylalanine incorporation, was studied under conditions of normoxia and anoxia in isolated perfused turtle [Trachemys (= Pseudemys) scripta elegans] hearts at 15 degrees C. Heart rate, cardiac output, and ventricular pressure development were unaffected by 2 or 3 h of anoxia. Despite the anoxia, energy levels in the heart were presumably still high, since contractility was maintained. RNA content of ventricle decreased after anoxic perfusion. Rates of total protein synthesis rates in ventricle were threefold lower under anoxia than under normoxia. These findings suggest that the total level of RNA is one determinant of protein synthesis. Incorporation of label into protein extracted from mitochondria was also assessed. The ratio of mitochondrial to whole ventricular protein synthesis was significantly lower after anoxia, revealing preferential control mechanisms under anoxia between the synthesis of total cellular protein and protein destined for mitochondria. Isolated mitochondria were still coupled after 2 or 3 h of anoxia. In effect, the mitochondria enter into a state of hypometabolism in terms of rates of ATP synthesis and protein synthesis, but functional integrity is maintained. The decrease in protein synthesis in general and mitochondrial protein synthesis in particular may represent an adaptation to allow the partitioning of the available energy resources toward mechanical function during anoxia.

scholarly journals Dependence of nucleus-directed rRNA synthesis upon mitochondrial protein synthesis in Tetrahymena.

1982 ◽  
Vol 2 (5) ◽  
pp. 508-516 ◽  
Author(s):  
L Ruben ◽  
A B Hooper
Keyword(s):  
Protein Synthesis ◽  
Rna Synthesis ◽  
Mitochondrial Protein ◽  
Tetrahymena Pyriformis ◽  
Cellular Protein ◽  
Rrna Synthesis ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Rrna ◽  
Polyadenylated Rna ◽  
Nuclear Rna

The antibiotic chloramphenicol selectively inhibited mitochondrial protein synthesis in the ciliate protozoan Tetrahymena pyriformis GL. Secondary to the inhibition of mitochondrial protein synthesis was an inhibition of nuclear RNA synthesis at a time before inhibition of cellular protein and DNA synthesis. Of the stable non-polyadenylated RNA species in Tetrahymena, the addition of chloramphenicol resulted specifically in the inhibition of synthesis of 28S + 17S and 5S rRNA transcripts. By contrast, syntheses of 4S tRNA and 21S mitochondrial rRNA were not as extensively inhibited. The addition of 60 microM hemin before the addition of chloramphenicol partially protected against the inhibition of RNA synthesis. These data indicate that continued synthesis of nucleus-directed rRNA is linked to the synthesis of mitochondrial proteins in Tetrahymena.

Dependence of nucleus-directed rRNA synthesis upon mitochondrial protein synthesis in Tetrahymena

1982 ◽  
Vol 2 (5) ◽  
pp. 508-516
Author(s):  
L Ruben ◽  
A B Hooper
Keyword(s):  
Protein Synthesis ◽  
Rna Synthesis ◽  
Mitochondrial Protein ◽  
Tetrahymena Pyriformis ◽  
Cellular Protein ◽  
Rrna Synthesis ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Rrna ◽  
Polyadenylated Rna ◽  
Nuclear Rna

The antibiotic chloramphenicol selectively inhibited mitochondrial protein synthesis in the ciliate protozoan Tetrahymena pyriformis GL. Secondary to the inhibition of mitochondrial protein synthesis was an inhibition of nuclear RNA synthesis at a time before inhibition of cellular protein and DNA synthesis. Of the stable non-polyadenylated RNA species in Tetrahymena, the addition of chloramphenicol resulted specifically in the inhibition of synthesis of 28S + 17S and 5S rRNA transcripts. By contrast, syntheses of 4S tRNA and 21S mitochondrial rRNA were not as extensively inhibited. The addition of 60 microM hemin before the addition of chloramphenicol partially protected against the inhibition of RNA synthesis. These data indicate that continued synthesis of nucleus-directed rRNA is linked to the synthesis of mitochondrial proteins in Tetrahymena.

scholarly journals Mitochondrial stress response triggered by defects in protein synthesis quality control

2019 ◽  
Vol 2 (1) ◽  
pp. e201800219 ◽  
Author(s):  
Uwe Richter ◽  
Kah Ying Ng ◽  
Fumi Suomi ◽  
Paula Marttinen ◽  
Taina Turunen ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Synthesis ◽  
Stress Response ◽  
Expression System ◽  
Mitochondrial Protein ◽  
Clinical Syndrome ◽  
Control Mechanisms ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Ribosomes ◽  
Form And Function

Mitochondria have a compartmentalized gene expression system dedicated to the synthesis of membrane proteins essential for oxidative phosphorylation. Responsive quality control mechanisms are needed to ensure that aberrant protein synthesis does not disrupt mitochondrial function. Pathogenic mutations that impede the function of the mitochondrial matrix quality control protease complex composed of AFG3L2 and paraplegin cause a multifaceted clinical syndrome. At the cell and molecular level, defects to this quality control complex are defined by impairment to mitochondrial form and function. Here, we establish the etiology of these phenotypes. We show how disruptions to the quality control of mitochondrial protein synthesis trigger a sequential stress response characterized first by OMA1 activation followed by loss of mitochondrial ribosomes and by remodelling of mitochondrial inner membrane ultrastructure. Inhibiting mitochondrial protein synthesis with chloramphenicol completely blocks this stress response. Together, our data establish a mechanism linking major cell biological phenotypes of AFG3L2 pathogenesis and show how modulation of mitochondrial protein synthesis can exert a beneficial effect on organelle homeostasis.

scholarly journals Translation of MT-ATP6 pathogenic variants reveals distinct regulatory consequences from the co-translational quality control of mitochondrial protein synthesis.

2021 ◽  
Author(s):  
Kah Ying Ng ◽  
Uwe Richter ◽  
Christopher Jackson ◽  
Sara Seneca ◽  
Brendan Battersby
Keyword(s):  
Quality Control ◽  
Protein Synthesis ◽  
Mitochondrial Gene ◽  
Mitochondrial Protein ◽  
Control Mechanisms ◽  
Mitochondrial Protein Synthesis ◽  
Primary Defect ◽  
Pathogenic Variants ◽  
Heterogenous Group ◽  
Quality Control Mechanism

Pathogenic variants that disrupt human mitochondrial protein synthesis are associated with a clinically heterogenous group of diseases. Despite an impairment in oxidative phosphorylation being a common phenotype, the underlying molecular pathogenesis is more complex than simply a bioenergetic deficiency. Currently, we have limited mechanistic understanding on the scope by which a primary defect in mitochondrial protein synthesis contributes to organelle dysfunction. Since the proteins encoded in the mitochondrial genome are hydrophobic and need co-translational insertion into a lipid bilayer, responsive quality control mechanisms are required to resolve aberrations that arise with the synthesis of truncated and misfolded proteins. Here, we show that defects in the OXA1L-mediated insertion of MT-ATP6 nascent chains into the mitochondrial inner membrane are rapidly resolved by the AFG3L2 protease complex. Using pathogenic MT-ATP6 variants, we then reveal discrete steps in this quality control mechanism and the differential functional consequences to mitochondrial gene expression. The inherent ability of a given cell type to recognize and resolve impairments in mitochondrial protein synthesis may in part contribute at the molecular level to the wide clinical spectrum of these disorders.

scholarly journals Bovine mitochondrial protein synthesis elongation factors

1989 ◽  
Vol 264 (32) ◽  
pp. 19125-19131
Author(s):  
C J Schwartzbach ◽  
L L Spremulli
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
Elongation Factors

scholarly journals Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 674
Author(s):  
Francesco Capriglia ◽  
Francesca Rizzo ◽  
Giuseppe Petrosillo ◽  
Veronica Morea ◽  
Giulia d’Amati ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Molecular Mechanisms ◽  
Mitochondrial Protein ◽  
Trna Synthetase ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Translation ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Mitochondrial Functions ◽  
Carboxy Terminal

The m.3243A>G mutation within the mitochondrial mt-tRNALeu(UUR) gene is the most prevalent variant linked to mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. This pathogenic mutation causes severe impairment of mitochondrial protein synthesis due to alterations of the mutated tRNA, such as reduced aminoacylation and a lack of post-transcriptional modification. In transmitochondrial cybrids, overexpression of human mitochondrial leucyl-tRNA synthetase (LARS2) has proven effective in rescuing the phenotype associated with m.3243A>G substitution. The rescuing activity resides in the carboxy-terminal domain (Cterm) of the enzyme; however, the precise molecular mechanisms underlying this process have not been fully elucidated. To deepen our knowledge on the rescuing mechanisms, we demonstrated the interactions of the Cterm with mutated mt-tRNALeu(UUR) and its precursor in MELAS cybrids. Further, the effect of Cterm expression on mitochondrial functions was evaluated. We found that Cterm ameliorates de novo mitochondrial protein synthesis, whilst it has no effect on mt-tRNALeu(UUR) steady-state levels and aminoacylation. Despite the complete recovery of cell viability and the increase in mitochondrial translation, Cterm-overexpressing cybrids were not able to recover bioenergetic competence. These data suggest that, in our MELAS cell model, the beneficial effect of Cterm may be mediated by factors that are independent of the mitochondrial bioenergetics.

The effect of inhibition of mitochondrial protein synthesis on the proliferation and phenotypic properties of a rat leukemia in different stages of in-vivo tumor development

1987 ◽  
Vol 11 (6) ◽  
pp. 529-536 ◽  
Author(s):  
Coby Van den Bogert ◽  
Bert H.J. Dontje ◽  
Štefan Kuẑela ◽  
Trudi E. Melis ◽  
Davine Opstelten ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Protein ◽  
Tumor Development ◽  
Mitochondrial Protein Synthesis ◽  
Phenotypic Properties
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