**3. DNA mitochondria and disease**

of average survival suggest that in animals treated with antioxidant therapy these can effectively, nonspecifically protect against various causes of early mortality [55, 56]. These protective effects can have great importance for the human population given that due to their living conditions humans live in an adverse environment and are subjected, for example, to radiation and toxic compounds, so they are exposed to damage by oxidative stress of exogenous

**Figure 6.** Mitochondrial dysfunction. The mitochondria are the main endogenous generator of free radicals. This production acts in a vicious circle that damages the mitochondria and therefore the mitochondrial primordial functions

as shown in the figure. This image is a modification of QIAGEN's original [Torres-Sánchez ED].

The animals would have regulatory mechanisms active during development that would monitor mitochondrial activity and, in response, establish the rates of respiration, behavior, and aging that persist during adult life [15, 60]. Although many of these studies have been carried out in experimental models, the results are relevant since they suggest that at least some of the interventions aimed at reducing the effects of aging should be considered in the early stages and not during the adult life of the individual [61]. Also, mitochondria that have suffered oxidative damage also contribute to the aging process [62–64]. Based on the studies that associate the increase of oxidative stress with aging, a line of research has been strengthened which proposes that the decrease in caloric intake is associated with an increase in the resistance of the central nervous system to suffer the neurodegenerative disorders of aging (**Figure 7**) [65]. The neuroprotective effect would depend on the decrease in the generation of oxygen radicals and an increase in the production of neurotrophic factors and protein

origin [57–59].

164 Mitochondrial DNA - New Insights

chaperones [66, 67].

Mitochondrial diseases are a group of disorders whose common feature is a defect in the production of ATP. However, this term is frequently applied to disorders caused by damage to the oxidative phosphorylation (OXPHOS) system because for many years only mutations in mtDNA related to these diseases had been detected. But, identification of nuclear genes encoding proteins of the OXPHOS system complexes, or responsible for their assembly, has been described [68].

Primary deficits of coenzyme Q10 (CoQ10) include various disorders caused by defects of their biosynthesis at different levels. The CoQ10 transports electrons from complexes I and II to complex III and receives electrons from the beta-oxidation pathway via electron-transferringflavoprotein dehydrogenase (ETFDH) [75]. There are at least nine enzymes necessary for the synthesis of CoQ10, and mutations in the genes that encode them are responsible for different cases of encephalomyopathies. There are also disorders due to CoQ10 secondary deficits, including autosomal recessive cases of cerebellar ataxia of unknown cause in children, apraxia syndrome with oculomotor ataxia 2 (AOA2) caused by mutations in the aprataxin gene (APTX), and myopathic form of glutaric aciduria type II (GAII) caused by mutations in the gene that encodes the ETFDH [76, 77]. The importance of knowledge of these disorders is that supplements with CoQ10 improve the symptoms in these patients. Defects have also been described in proteins involved in the assembly of complex III (BCS1L) and complex V (ATPAF2) [3, 74].

Mitochondrial Aging and Metabolism: The Importance of a Good Relationship in the Central…

http://dx.doi.org/10.5772/intechopen.76652

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These diseases are due to defects in nuclear factors involved in the replication, maintenance, and translation of mtDNA. The resulting disorders are characterized by quantitative alterations (depletion syndromes) or qualitative alterations (multiple deletions) of mtDNA or by defects in the translation of respiratory chain components encoded in the mtDNA. Thus, many of these disorders are due to alterations in the pool of nucleotides necessary for the synthesis of mtDNA or in the enzymes necessary for the replication of

**Figure 8.** Multiple deletions of mtDNA. Mitochondrial damage is regulated by multiple deletions in the PEO, ANT1, ECGF I, POLG, and OLG2 genes. The deletions will trigger the syndromes and signs that are illustrated in the image.

This image is a modification of QIAGEN's original [Torres-Sánchez ED].

**4.2. Diseases secondary to defects in intergenomic communication**

mtDNA itself [78, 79].

Mitochondrial disease can associate with any symptom, in any organ, at any age, but some symptoms and signs are actually more suggestive of a mitochondrial disorder than others. These "warning signs" warrant the onset of a diagnostic assessment of mitochondrial diseases. In contrast, numerous nonspecific symptoms occur frequently in infants and children with mitochondrial disease, but they have a broad differential diagnosis and lead more often to other diagnoses [68]. For example, pigmentary retinopathy in a preadolescent child may be a trait of mitochondrial disease but should suggest the possibility of juvenile neuronal ceroid lipofuscinosis or another genetic syndrome. Thus, nonspecific symptoms, especially isolated ones, do not indicate per se a mitochondrial problem. However, when combined, the likelihood of mitochondrial disorder increases, especially if the nonspecific aspects affect different organ systems, which leads to the initiation of appropriate initial diagnostic investigations [53, 69].

The defects of the respiratory chain of Mendelian inheritance are included in four groups:

