scholarly journals Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 173
Author(s):  
Panagiotis Karakaidos ◽  
Theodoros Rampias
Keyword(s):  
Mitochondrial Dna ◽  
Protein Synthesis ◽  
Mitochondrial Genome ◽  
Aging Process ◽  
Mitochondrial Protein ◽  
Eukaryotic Cells ◽  
Mitochondrial Protein Synthesis ◽  
Respiratory Chain Complexes ◽  
Chain Complexes ◽  
Insight Into

In eukaryotic cells, mitochondria originated in an α-proteobacterial endosymbiont. Although these organelles harbor their own genome, the large majority of genes, originally encoded in the endosymbiont, were either lost or transferred to the nucleus. As a consequence, mitochondria have become semi-autonomous and most of their processes require the import of nuclear-encoded components to be functional. Therefore, the mitochondrial-specific translation has evolved to be coordinated by mitonuclear interactions to respond to the energetic demands of the cell, acquiring unique and mosaic features. However, mitochondrial-DNA-encoded genes are essential for the assembly of the respiratory chain complexes. Impaired mitochondrial function due to oxidative damage and mutations has been associated with numerous human pathologies, the aging process, and cancer. In this review, we highlight the unique features of mitochondrial protein synthesis and provide a comprehensive insight into the mitonuclear crosstalk and its co-evolution, as well as the vulnerabilities of the animal mitochondrial genome.

scholarly journals Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation

2008 ◽  
Vol 181 (7) ◽  
pp. 1117-1128 ◽  
Author(s):  
Robert W. Gilkerson ◽  
Eric A. Schon ◽  
Evelyn Hernandez ◽  
Mercy M. Davidson
Keyword(s):  
Mitochondrial Dna ◽  
Protein Synthesis ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Mitochondrial Protein ◽  
Functional Complementation ◽  
Mitochondrial Protein Synthesis ◽  
Protein Assemblies ◽  
Mtdna Mutations ◽  
Mitochondrial Nucleoids

Mitochondrial DNA (mtDNA) is packaged into DNA-protein assemblies called nucleoids, but the mode of mtDNA propagation via the nucleoid remains controversial. Two mechanisms have been proposed: nucleoids may consistently maintain their mtDNA content faithfully, or nucleoids may exchange mtDNAs dynamically. To test these models directly, two cell lines were fused, each homoplasmic for a partially deleted mtDNA in which the deletions were nonoverlapping and each deficient in mitochondrial protein synthesis, thus allowing the first unequivocal visualization of two mtDNAs at the nucleoid level. The two mtDNAs transcomplemented to restore mitochondrial protein synthesis but were consistently maintained in discrete nucleoids that did not intermix stably. These results indicate that mitochondrial nucleoids tightly regulate their genetic content rather than freely exchanging mtDNAs. This genetic autonomy provides a molecular mechanism to explain patterns of mitochondrial genetic inheritance, in addition to facilitating therapeutic methods to eliminate deleterious mtDNA mutations.

scholarly journals In vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria.

1991 ◽  
Vol 11 (4) ◽  
pp. 2236-2244 ◽  
Author(s):  
A Chomyn ◽  
G Meola ◽  
N Bresolin ◽  
S T Lai ◽  
G Scarlato ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Protein Synthesis ◽  
Human Cell ◽  
Mitochondrial Myopathy ◽  
Mitochondrial Protein ◽  
Human Cell Lines ◽  
Mitochondrial Protein Synthesis ◽  
Direct Link ◽  
Genetic Transfer

A severe mitochondrial protein synthesis defect in myoblasts from a patient with mitochondrial myopathy was transferred with myoblast mitochondria into two genetically unrelated mitochondrial DNA (mtDNA)-less human cell lines, pointing to an mtDNA alteration as being responsible and sufficient for causing the disease. The transfer of the defect correlated with marked deficiencies in respiration and cytochrome c oxidase activity of the transformants and the presence in their mitochondria of mtDNA carrying a tRNA(Lys) mutation. Furthermore, apparently complete segregation of the defective genotype and phenotype was observed in the transformants derived from the heterogeneous proband myoblast population, suggesting that the mtDNA heteroplasmy in this population was to a large extent intercellular. The present work thus establishes a direct link between mtDNA alteration and a biochemical defect.

Mitochondrial DNA Medicine

2007 ◽  
Vol 27 (1-3) ◽  
pp. 5-9 ◽  
Author(s):  
Salvatore DiMauro
Keyword(s):  
Mitochondrial Dna ◽  
Protein Synthesis ◽  
Mitochondrial Protein ◽  
Point Mutations ◽  
Specific Protein ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Genetics ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Mitochondrial Medicine

The small, maternally inherited mitochondrial DNA (mtDNA) has turned out to be a hotbed of pathogenic mutations: 15 years into the era of ‘mitochondrial medicine’, over 150 pathogenic point mutations and countless rearrangements have been associated with a variety of multisystemic or tissue-specific human diseases. MtDNA-related disorders can be divided into two major groups: those due to mutations in genes affecting mitochondrial protein synthesis in toto and those due to mutations in specific protein-coding genes. Here we review the mitochondrial genetics and the clinical features of the mtDNA-related diseases.

scholarly journals EXPRESSION OF THE MITOCHONDRIAL GENOME IN HELA CELLS

1973 ◽  
Vol 56 (3) ◽  
pp. 819-831 ◽  
Author(s):  
Brian Storrie ◽  
Giuseppe Attardi
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Genome ◽  
Hela Cells ◽  
Mitochondrial Protein ◽  
Selective Inhibition ◽  
Mitochondrial Protein Synthesis ◽  
Cloning Efficiency ◽  
Cell Growth Inhibition ◽  
Progressive Loss ◽  
Two Generations

The effect of selective inhibition of mitochondrial protein synthesis by chloramphenicol at 40 or 200 µg/ml on the formation of mitochondria in HeLa cells was investigated. HeLa cells, under the conditions used in the present work, grow at a decreasing rate for at least four cell generations in the presence of 40 µg/ml chloramphenicol, and for two generations in the presence of 200 µg/ml chloramphenicol. The progressive cell growth inhibition which begins after 2 days of exposure of the cells to 40 µg/ml chloramphenicol is immediately or gradually reversible, upon removal of the drug, for periods up to at least 8 days of treatment, though there is a progressive loss of cloning efficiency. In cells which have been treated for 6–7 days with 40 or 200 µg/ml of chloramphenicol, mitochondrial protein synthesis occurs at a normal or near-normal rate 1 h after removal of the drug. Mitochondria increase normally in number and show a normal size and amount of cristae in the presence of either concentration of drug. However, in 4–5% of the mitochondrial profiles the cristae appear to be arranged in unusual, circular, looped or whorled configuration.

scholarly journals In vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria

1991 ◽  
Vol 11 (4) ◽  
pp. 2236-2244
Author(s):  
A Chomyn ◽  
G Meola ◽  
N Bresolin ◽  
S T Lai ◽  
G Scarlato ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Protein Synthesis ◽  
Human Cell ◽  
Mitochondrial Myopathy ◽  
Mitochondrial Protein ◽  
Human Cell Lines ◽  
Mitochondrial Protein Synthesis ◽  
Direct Link ◽  
Genetic Transfer

A severe mitochondrial protein synthesis defect in myoblasts from a patient with mitochondrial myopathy was transferred with myoblast mitochondria into two genetically unrelated mitochondrial DNA (mtDNA)-less human cell lines, pointing to an mtDNA alteration as being responsible and sufficient for causing the disease. The transfer of the defect correlated with marked deficiencies in respiration and cytochrome c oxidase activity of the transformants and the presence in their mitochondria of mtDNA carrying a tRNA(Lys) mutation. Furthermore, apparently complete segregation of the defective genotype and phenotype was observed in the transformants derived from the heterogeneous proband myoblast population, suggesting that the mtDNA heteroplasmy in this population was to a large extent intercellular. The present work thus establishes a direct link between mtDNA alteration and a biochemical defect.

scholarly journals Reversible Inhibition of Mitochondrial Protein Synthesis during Linezolid-Related Hyperlactatemia

2006 ◽  
Vol 51 (3) ◽  
pp. 962-967 ◽  
Author(s):  
Glòria Garrabou ◽  
Alejandro Soriano ◽  
Sònia López ◽  
Jordi P. Guallar ◽  
Marta Giralt ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Protein Synthesis ◽  
Mononuclear Cells ◽  
Intact Cell ◽  
Mitochondrial Protein ◽  
Mitochondrial Rna ◽  
Mitochondrial Protein Synthesis ◽  
Peripheral Blood Mononuclear ◽  
Mitochondrial Mass ◽  
Clinical Recovery

ABSTRACT The objective of the present study was to determine the mitochondrial toxicity mechanisms of linezolid-related hyperlactatemia. Five patients on a long-term schedule of linezolid treatment were studied during the acute phase of hyperlactatemia and after clinical recovery and lactate normalization following linezolid withdrawal. Mitochondrial studies were performed with peripheral blood mononuclear cells and consisted of measurement of mitochondrial mass, mitochondrial protein synthesis homeostasis (cytochrome c oxidase [COX] activity, COX-II subunit expression, COX-II mRNA abundance, and mitochondrial DNA [mtDNA] content), and overall mitochondrial function (mitochondrial membrane potential and intact-cell oxidative capacity). During linezolid-induced hyperlactatemia, we found extremely reduced protein expression (16% of the remaining content compared to control values [100%], P < 0.001) for the mitochondrially coded, transcribed, and translated COX-II subunit. Accordingly, COX activity was also found to be decreased (51% of the remaining activity, P < 0.05). These reductions were observed despite the numbers of COX-II mitochondrial RNA transcripts being abnormally increased (297%, P = 0.10 [not significant]) and the mitochondrial DNA content remaining stable. These abnormalities persisted even after the correction for mitochondrial mass, which was mildly decreased during the hyperlactatemic phase. Most of the mitochondrial abnormalities returned to control ranges after linezolid withdrawal, lactate normalization, and clinical recovery. Linezolid inhibits mitochondrial protein synthesis, leading to decreased mitochondrial enzymatic activity, which causes linezolid-related hyperlactatemia, which resolves upon discontinuation of linezolid treatment.

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