scholarly journals Mitochondrial dysfunction and the role of the non-specialist laboratory

2002 ◽  
Vol 39 (5) ◽  
pp. 456-463 ◽  
Author(s):  
Maggie R Hancock
Keyword(s):  
Mitochondrial Dna ◽  
Oxidative Phosphorylation ◽  
Highly Active Antiretroviral Therapy ◽  
Nuclear Dna ◽  
Nuclear Genome ◽  
Mitochondrial Disorders ◽  
Highly Active ◽  
Clinical Presentations ◽  
Immunodeficiency Virus

Each human cell contains at least 1000 mitochondria, each containing several copies of mitochondrial DNA. This DNA is tiny compared with the nuclear genome, and its structure and products have been fully elucidated. Whilst oxidative phosphorylation depends on the polypeptides encoded by mitochondrial DNA, it also requires a huge number of nuclear DNA products. Inherited deleterious mutations of mitochondrial DNA leading to inefficient oxidative phosphorylation have been described as 'mitochondrial disorders', with a variety of clinical presentations. When similar clinical presentations occur with no discernible mutation of mitochondrial DNA, histological and biochemical evidence is required for diagnosis. The number of these laboratory-proven inherited mitochondrial disorders is growing. It is also becoming clear that mitochondrial DNA defects can be acquired, the most common cause being therapy with highly active antiretroviral therapy (HAART) for human immunodeficiency virus-1 (HIV-1) infection. Whilst definitive diagnosis of inherited or acquired mitochrondrial dysfunction requires access to specialist laboratory techniques, routine laboratories have a role to play in the initial investigation and monitoring of these conditions.

scholarly journals The Three Genetics (Nuclear DNA, Mitochondrial DNA, and Gut Microbiome) of Longevity in Humans Considered as Metaorganisms

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Paolo Garagnani ◽  
Chiara Pirazzini ◽  
Cristina Giuliani ◽  
Marco Candela ◽  
Patrizia Brigidi ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Complex Dynamics ◽  
Nuclear Genome ◽  
Holistic Approach ◽  
Human Longevity ◽  
Human Lifespan ◽  
Complex Interactions ◽  
Age Related

Usually the genetics of human longevity is restricted to the nuclear genome (nDNA). However it is well known that the nDNA interacts with a physically and functionally separated genome, the mitochondrial DNA (mtDNA) that, even if limited in length and number of genes encoded, plays a major role in the ageing process. The complex interplay between nDNA/mtDNA and the environment is most likely involved in phenomena such as ageing and longevity. To this scenario we have to add another level of complexity represented by the microbiota, that is, the whole set of bacteria present in the different part of our body with their whole set of genes. In particular, several studies investigated the role of gut microbiota (GM) modifications in ageing and longevity and an age-related GM signature was found. In this view, human being must be considered as “metaorganism” and a more holistic approach is necessary to grasp the complex dynamics of the interaction between the environment and nDNA-mtDNA-GM of the host during ageing. In this review, the relationship between the three genetics and human longevity is addressed to point out that a comprehensive view will allow the researchers to properly address the complex interactions that occur during human lifespan.

Incidence of Non–AIDS-Defining Cancers Before and During the Highly Active Antiretroviral Therapy Era in a Cohort of Human Immunodeficiency Virus–Infected Patients

2003 ◽  
Vol 21 (18) ◽  
pp. 3447-3453 ◽  
Author(s):  
Magid Herida ◽  
Murielle Mary-Krause ◽  
Régis Kaphan ◽  
Jacques Cadranel ◽  
Isabelle Poizot-Martin ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Potential Role ◽  
Hospital Database ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
French Hospital ◽  
French Hospital Database ◽  
Age And Sex

Purpose: To determine incidence of non–AIDS-defining cancers (NADC) in HIV–infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. Patients and Methods: Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. Results: NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin’s disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. Conclusion: Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.

scholarly journals The Role of Mitochondria in Carcinogenesis

2021 ◽  
Vol 22 (10) ◽  
pp. 5100
Author(s):  
Paulina Kozakiewicz ◽  
Ludmiła Grzybowska-Szatkowska ◽  
Marzanna Ciesielka ◽  
Jolanta Rzymowska
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Dna Polymorphisms ◽  
Gene Encoding ◽  
Dna Mutations ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Gene Coi ◽  
The Impact

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

scholarly journals Mitochondrial DNA Methylation and Human Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4594
Author(s):  
Andrea Stoccoro ◽  
Fabio Coppedè
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Nuclear Genome ◽  
Epigenetic Modifications ◽  
Human Diseases ◽  
Loop Region ◽  
D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

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