Pre-implantation genetic diagnosis
Sheila A.M. McLean, Sarah Elliston in Regulating Pre-Implantation Genetic Diagnosis, 2012
Mitochondria are the energy-producing organelles in the cytoplasm of every mammalian cell and contain small amounts of DNA. The inheritance and regulation of this mitochondrial DNA (mtDNA) is different from information that is inherited as chromosomes in the nucleus of the cell. First, mtDNA is transmitted solely from the mother in the egg (maternally inherited), and second, its usual function is dependent on the amount or nature of the mitochondria in each cell. Mitochondria containing either mutant or normal mtDNA may exist within the same cell (heteroplasmy), or all the mtDNA may all be the same (homoplasmy), either mutant or normal. The severity of most mitochondrial genetic diseases is dictated by the proportion of mutant to normal mitochondria within the cells, and that proportion may deteriorate in favour of disease with time. Thus, many of these diseases may manifest late or may increase in severity with age. There may also be variations in heteroplasmy between tissues, perhaps resulting in specific manifestations of the disease according to the most affected organ or system. The worst forms of mitochondrial disease may be associated with totally abnormal mitochondria; homoplasmic for a particular mutation.49
The Cell and Cell Division
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Mitochondria and chloroplasts contain the DNA that encodes the crucial structural and functional proteins, which permit the mitochondria to divide during cell division. Mitochondrial DNA utilizes biochemically distinct pathways from those of nuclear DNA. For instance, protein synthesis taking place in the cytoplasm but directed by nuclear DNA is blocked by cyclohexidine, whereas protein synthesis directed by mitochondrial DNA is blocked by chloramphenicol, erythromycin, and tetracycline. Mitochondria are not synthesized de novo, but arise from division of the organelle, which occurs during mitosis and is driven by mitochondrial DNA. Mitochondrial DNA is a circular structure like that of bacteria; in mammalian cells, it contains around 16.5 kbp. It synthesizes 2 ribosomal RNAs, 22 transfer RNAs (tRNAs), and 13 peptides. Unlike nuclear DNA, most of the nucleotides are direct coding sequences with little or no space left for regulatory codons (Table 1). Analysis of the genetic code shows that the codon sequence is relaxed, allowing many tRNA molecules to recognize any one of four nucleotides in the third or “wobble’’ position. In addition, in man, 3 of the 64 codons have different meanings from the standard codons.
Stroke
Henry J. Woodford in Essential Geriatrics, 2022
Mitochondria were originally symbiotic bacteria that migrated into animal cells with the advantage of being able to perform aerobic metabolism. They possess their own DNA and are inherited by the division of the mitochondria contained with the maternal egg cell. Various disorders have been described relating to mutations in mitochondrial DNA.128 One of these is ‘mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes' (MELAS). This disorder is very rare and usually presents in children or young adults with focal neurological deficits, seizures and progressive cognitive impairment. There may be an associated history of exercise intolerance, deafness, diabetes, migraine and/or learning disability. Fasting plasma and CSF lactate levels are elevated. Muscle biopsy may demonstrate ragged red fibres or abnormal mitochondria. There is no treatment for this condition.
Targeting mitochondrial quality control for treating sarcopenia: lessons from physical exercise
Published in Expert Opinion on Therapeutic Targets, 2019
Anna Picca, Riccardo Calvani, Christiaan Leeuwenburgh, Hélio José Coelho-Junior, Roberto Bernabei, Francesco Landi, Emanuele Marzetti
The generation of new mitochondria is attained through the coordinated expression of nuclear and mitochondrial DNA encoded genes (Figure 1). The process is orchestrated by members of the peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 (PGC-1) family of transcriptional co-activators, namely PGC-1α and PGC-1β (reviewed in [18]). Their interaction with several transcription factors [i.e., nuclear respiratory factors 1 and 2 (NRF1 and NRF2), estrogen-related receptor alpha (ERRα), and the PPAR family of transcription factors] regulates the expression of mitochondrial proteins, including mitochondrial transcription factor A (TFAM) and B2 (TFB2M) (reviewed in [18]). Once synthesized, TFAM and TFB2M are imported into the mitochondrion where they serve important housekeeping activities [18]. Specifically, TFAM binds to mitochondrial DNA (mtDNA) either as a histone-like protein that unwinds and bends mtDNA or to specific non-coding regions (NCRs) [19]. Dysregulation of TFAM binding to NCRs has been indicated as a potential mechanism underlying the impairment of mitochondrial biogenesis in aged rat tissues, including the skeletal muscle [20]. Recent evidence also indicates that TFAM binds more avidly to oxidized D-loop regions, the major site of transcriptional regulation, and contributes to impairing mitochondrial function in the aged heart [21]. Whether such a mechanism plays a role in the setting of muscle aging is yet to be established.
Genetic variations as molecular diagnostic factors for idiopathic male infertility: current knowledge and future perspectives
Published in Expert Review of Molecular Diagnostics, 2021
Mohammad Karimian, Leila Parvaresh, Mohaddeseh Behjati
Mitochondria have a significant effect on all biochemical pathways including sperm motility, which is strongly dependent on the ATP produced by oxidative phosphorylation in the mitochondrial sheath [116,117]. Mitochondria are located in the middle segment of the sperm. Mitochondrial DNA (mtDNA) contains several genes encoding the basic units of the respiratory chain in the mitochondrial inner membrane. It also encodes 22 tRNAs and 2 rRNAs that are essential for protein synthesis [118]. The human mtDNA gene is intron-less and devoid of histones or DNA-binding proteins. The gene is rapidly replicated without the presence of efficient transcription and DNA repair mechanisms, which increases the occurrence of mtDNA mutation by 10- to 100-fold over the DNA of the nucleus. Some studies have suggested that point mutations and deletions in mtDNA can decrease male sperm motility and subsequent development of male fertility [119]. The most common type of deletions present in mtDNA is the 4977-bp deletion, that about one-third of the mtDNA length is lost resulting in the fusion of ATPase8 and ND5 genes. This process may impair mitochondrial respiratory function and decrease ATP synthesis [120].
Mitochondrial C4375T mutation might be a molecular risk factor in a maternal Chinese hypertensive family under haplotype C
Published in Clinical and Experimental Hypertension, 2018
Hong Chen, Min Sun, Zhen Fan, Maoqing Tong, Guodong Chen, Danhui Li, Jihui Ye, Yumin Yang, Yongding Zhu, Jianhua Zhu
In this present study, we have exhibited the genetic, clinical, molecular characterization of one Han Chinese hypertension pedigree deeply. The proband suffered hypertension from 66 years old, and as time went by, he was attacked by EH’s complication cerebrovascular accident and died 3 months later after our test. Collected his genetic history data, we found his family members exhibited matrilineal inheritance. It suggested that matrilineal genetic mode might play a bigger role in this family. So, we investigated in depth of this family. There were 60 participates in this family, 4 of whom were died, including 34 men and 26 women, 9 of whom suffered hypertension. Not only the family exhibit typical matrilineal transmission, statistical analysis and clinical phenotype reveal mitochondrial DNA mutations may play a role in this family. The penetrance of matrilineal members is 32% (8 in 25), while the penetrance of nonmatrilineal members is 2.8% (1 in 35, P < 0.05). It shows statistically significant difference. Clinically, mean onset age of each generation decreased gradually. So, it suggests mitochondrial DNA change is probably the molecular reason for this family.
Related Knowledge Centers
- Chloroplast
- DNA
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- Cell Nucleus
- Organelle
- Mitochondrion
- Adenosine Triphosphate
- Base Pair