scholarly journals MrpL35, a mitospecific component of mitoribosomes, plays a key role in cytochrome c oxidase assembly

2017 ◽  
Vol 28 (24) ◽  
pp. 3489-3499 ◽  
Author(s):  
Jodie M. Box ◽  
Jasvinder Kaur ◽  
Rosemary A. Stuart
Keyword(s):  
Protein Synthesis ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
Regulatory Subunits ◽  
The Core ◽  
Yeast Strains ◽  
Oxphos System ◽  
Core Components

Mitoribosomes perform the synthesis of the core components of the oxidative phosphorylation (OXPHOS) system encoded by the mitochondrial genome. We provide evidence that MrpL35 (mL38), a mitospecific component of the yeast mitoribosomal central protuberance, assembles into a subcomplex with MrpL7 (uL5), Mrp7 (bL27), and MrpL36 (bL31) and mitospecific proteins MrpL17 (mL46) and MrpL28 (mL40). We isolated respiratory defective mrpL35 mutant yeast strains, which do not display an overall inhibition in mitochondrial protein synthesis but rather have a problem in cytochrome c oxidase complex (COX) assembly. Our findings indicate that MrpL35, with its partner Mrp7, play a key role in coordinating the synthesis of the Cox1 subunit with its assembly into the COX enzyme and in a manner that involves the Cox14 and Coa3 proteins. We propose that MrpL35 and Mrp7 are regulatory subunits of the mitoribosome acting to coordinate protein synthesis and OXPHOS assembly events and thus the bioenergetic capacity of the mitochondria.

Oxytetracycline inhibition of mitochondrial protein synthesis in bovine lymphocytes infected withTheileria parvaor stimulated by mitogen

Parasitology ◽  
1990 ◽  
Vol 101 (3) ◽  
pp. 387-393 ◽  
Author(s):  
P. R. Spooner
Keyword(s):  
Protein Synthesis ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Oxidase Activity ◽  
Mitochondrial Protein ◽  
Inhibitory Effect ◽  
Mitochondrial Protein Synthesis ◽  
Drug Concentrations ◽  
Bovine Lymphocytes

SUMMARYOxytetracycline (OTC) significantly inhibited cytochrome c oxidase activity in bovine lymphocytes infected withTheileria parvaand in uninfected mitogen-stimulated lymphocytes. The inhibitory effect was detectedin vitrowithin 24 h of treatment with drug concentrations as low as 1 µg/ml. Following mitogen stimulation of lymphocytes, concentrations of 3 and 10 µg/ml OTC completely inhibited an increase in cytochrome c oxidase activity for 48–72 h. This inhibitory activity was considered to be due to a direct effect on lymphoblast mitochondrial protein synthesis. As a consequence, adenosine triphosphate activity was significantly reduced in lymphocytes stimulated either by infection withT. parvasporozoites or by mitogen and then treated with OTC. The results also indicated that parasite mitochondrial protein synthesis was inhibited by OTC. The activity of OTC reported in this study could explain the suppression of disease following ‘infection and treatment’ immunization against East Coast fever and thein vitrodrug-inhibition of schizont development.

scholarly journals Ischemia-reperfusion induces inhibition of mitochondrial protein synthesis and cytochrome c oxidase activity in rat hippocampus

2009 ◽  
pp. 127-138
Author(s):  
P Racay ◽  
Z Tatarková ◽  
A Drgová ◽  
P Kaplan ◽  
D Dobrota
Keyword(s):  
Protein Synthesis ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Brain Ischemia ◽  
Ischemia Reperfusion ◽  
Mitochondrial Protein ◽  
Neuronal Cell ◽  
Northern Hybridization ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Translation

Dysfunction of mitochondria induced by ischemia is considered to be a key event triggering neuronal cell death after brain ischemia. Here we report the effect of ischemia-reperfusion on mitochondrial protein synthesis and activity of cytochrome c oxidase (EC 1.9.3.1, COX). By performing 4-vessel occlusion model of global brain ischemia, we have observed that 15 min of global ischemia led to the inhibition of COX subunit I (COXI) synthesis to 56 % of control. After 1, 3 and 24 h of reperfusion, COXI synthesis was inhibited to 46, 50 and 72 % of control, respectively. Depressed synthesis of COXI was not a result of either diminished transcription of COXI gene or increased proteolytic degradation of COXI, since both Northern hybridization and Western blotting did not show significant changes in COXI mRNA and protein level. Thus, ischemiareperfusion affects directly mitochondrial translation machinery. In addition, ischemia in duration of 15 min and consequent 1, 3 and 24 h of reperfusion led to the inhibition of COX activity to 90.3, 80.3, 81.9 and 83.5 % of control, respectively. Based on our data, we suggest that inhibition of COX activity is rather caused by ischemia-induced modification of COX polypeptides than by inhibition of mitochondrial translation.

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.

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