**2.1 Mitochondria and physiological functions**

Mitochondria are essential organelle which accommodate in their inner membrane large numbers of five oxidative phosphorylation complexes (complexes I–V). They are the only organelles containing their own genome – the mitochondrial DNA (mtDNA). The latter encodes proteins essential to electron flow through a series of protein complexes called the respiratory chain (also known as electron transport chain, or ETC) [6].

Perturbations in mitochondrial structure and function include impaired replication, alterations in mtDNA copy number, increased ROS production, mtDNA mutations and organelle damage [7].

Mitochondrial complex I, a key component of the ETC, aerobically oxidizes NADH in the ETC to generate ATP. The principal function of mitochondria is to use products of glycolysis, proteolysis, or lipolysis and oxygen through biochemical reactions leading to ATP formation [8]. The origin of heat in the human body is the free energy released during the chemical breakdown of molecules. In fact, the main mechanism of heat production and thermoregulation consists in uncoupling chemical reactions in the mitochondrial matrix from ATP synthesis, a phenomenon called "mitochondrial uncoupling". ATP hydrolysis by the NA+ /K+ ATPase is also a substantial source of heat which is thought to contribute to thermogenesis [9]. Mitochondria have also emerged as major players in steroid hormone actions and to sequester Ca2+ ions to contain that process, as well as to express genes in order to regulate important cell functions [7]. Disruption of mitochondrial homeostasis contributes to the pathogenesis of many disorders, including neurodegeneration, myocardial infarction, cancer, and metabolic diseases [10].

## **2.2 Stress exposure: implication for mitochondria function**

ROS include many species such as superoxide (O2 •−) and hydroxyl (OH• ) radicals, hydrogen peroxide (H2O2) and peroxynitrite (ONOO•−), the result of the reaction of superoxide with nitric oxide (NO) [11]. The excessive formation of ROS and the impairment of defensive antioxidant systems lead to oxidative stress. Under severe or prolonged exposure to a stressful condition, mitochondria become fragmented, increasing the risk of cell death [12]. Prolonged fragmentation leads to pronounced oxidative stress and mitochondrial DNA damage [13].

The initial formation of mitochondrial reactive oxygen and nitrogen species can also activate secondary sources of oxidants involving permeability transition pore [14]. The main endogenous process that generates ROS is oxidative phosphorylation [15]. Initial

*Oxidative Stress and Cardiovascular Diseases: The Role of Mitochondria DOI: http://dx.doi.org/10.5772/intechopen.103979*

ROS production can induce specific cell signaling pathways mediated by protein phosphorylation and transcriptional factors such as NO synthase and NRF2 (transcription factor nuclear factor erythroid 2), that could later provide a feed-back to downregulate ROS production [16, 17].

The regulation of mitochondrial ROS generation and their levels is exerted by a number of factors, such as the redox state of respiratory components and oxygen tension [18]. Mitochondria have unique redox-related enzymes and transporters such as glutaredoxin 2, which functions to catalyze reversible oxidation and glutathionylation of mitochondrial membrane proteins as well as protecting from oxidative stress and apoptosis [19]. Therefore, we suggest a strong connection between mitochondrial dysfunction and oxidative stress.

Biomarkers of oxidative stress include the products of lipid peroxidation, malondialdehyde (MDA) and protein oxidation (advanced oxidation protein products, AOPP) [20]. Extensive lipid peroxidation in biological membranes can lead to disturbances of structural integrity, a loss of fluidity, a decrease of membrane potential, and an increase of permeability to ions. Moreover, enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) also serve as biomarkers of oxidative insult. SOD is recognized as a primary line of defense mechanism in the antioxidant system by catalyzing the dismutation of superoxide radicals (O2 •−) into molecular oxygen (O2) and H2O2. This latter is neutralized by the combined action of CAT and GPx in all vertebrates [21]. Some proteins, such as secretory IgA and heat shock proteins (HSPs), serve as indicators of immunity or resistance mechanisms to stress. An alteration in biomarkers can reflect the severity of deviation from normality or the degree of damage.
