**2. Mitochondrial physiology and ROS production**

Mitochondria, cellular organelles in cells of eukaryotic organisms, have a primarily role in the process of pyruvate breakdown and ATP synthesis, generating water and carbon dioxide (CO2) as the end products via aerobic respiration [21]. Mitochondria turned into driving forces in biological evolution after the symbiotic engulfment of aerobic α-proteobacteria by a precursor of the eukaryotic cells around 2 billion years ago [22, 23]. Although mitochondria have preserved the double-membrane shape and ATP production characters of their ancestors, they have attained numerous additional functions in the cell, dramatically altering their structure and composition [24]. Most part of the bacterial genome was rapidly lost or transferred to the nuclear DNA [25]. Mammalian mitochondrial genome is transmitted solely through the female germ line [26]. Human mitochondrial DNA (mtDNA) is a double-stranded, circular molecule of 16,569 bp and contains 37 genes coding for two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and 13 proteins [22]. As the major power plants, mitochondria constantly produce reactive radical oxidants as byproducts during OXPHOS. Thus, in response to the metabolic or environmental stresses, mitochondria have accomplished antioxidant defence system [27]. Mitochondria are also highly dynamic to maintain the functions, which form a tubular network that continually changes by fission and fusion [28]. In this section, we concisely discuss overall mitochondrial biology and the ROS generation.

#### **2.1 Mitochondrial structure and genome**

A mitochondrion comprises four subcompartments, the outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM), and the two soluble compartments intermembrane space (IMS) and matrix, which are architecturally and functionally distinct. The OMM encloses the organelle, which has a proteinto-phospholipid ratio similar to that of the plasma membrane [29]. It contains

**13**

**Figure 1.**

*Mitochondrial structure.*

*Physiological Functions of Mitochondrial Reactive Oxygen Species*

large numbers of integral membrane protein, porin [30]. Voltage-dependent anion channel (VDAC) is a major trafficking protein that forms a beta barrel spanning the outer membrane, which transports nucleotides, ions and metabolites between cytosol and intermembrane space [31, 32]. The IMM is found inside of the OMM, which encloses mitochondrial matrix, extensively folded and compartmentalized [33]. The IMM is non-permeable to nucleotides, sugars and small ions; thus specific

carrier proteins enable the molecules to transport across the membrane [34]. The mitochondrial respiratory complexes I–IV, in which electrochemical gradient is generated for OXPHOS to occur for ATP synthesis, are embedded in the IMM [22]. Mitochondria contain two aqueous compartments: the IMS and matrix. The IMS, existing between the OMM and IMM, relays molecular transport from cytosol to mitochondrial matrix or reversely [35]. The compositions of small molecules such as ions and sugars in IMS are chemically similar to those in cytosol, as OMM is selectively permeable to those molecules [36]. However, in case of large proteins, the specific signalling peptides are required to be transported across the OMM. Thus, the protein composition of the IMS is different to the protein composition of the cytosol (e.g. cytochrome c) [37]. The mitochondrial matrix, enclosed by IMM, contains mitochondrial DNA (mtDNA), RNA and proteins. Especially, a number of proteins in the matrix are involved in diverse biochemical processes such as tricarboxylic acid (TCA) cycle, fatty acid oxidation, amino acid degradation and

mitochondrial dynamics (fission and fusion) [27, 38] (**Figure 1**).

Mitochondria contain their own genetic material (mtDNA), which is maternally inherited without DNA recombination and encodes 37 genes that participate in mitochondrial ATP synthesis. Thirteen genes of them are involved in OXPHOS, and the rest two rRNAs and 22 tRNAs. One human cell has hundreds to thousands of mtDNA copies [39, 40]. mtDNA has high rates of mutation and sequence evolution, and mutant and wild-type mtDNA are present in the cell at different proportions [41, 42]. The mtDNA mutations lead to abnormality in OXPHOS activity and ATP synthesis [43]. The mtDNA is exposed to OXPHOS-derived ROS without conventional histone proteins. Moreover, in the lacking repair mechanisms, mtDNA damage further amplifies during DNA replication [44]. Therefore, the mtDNA is susceptible to mutation

**2.2 Mitochondrial genome**

*DOI: http://dx.doi.org/10.5772/intechopen.88386*

#### *Physiological Functions of Mitochondrial Reactive Oxygen Species DOI: http://dx.doi.org/10.5772/intechopen.88386*

large numbers of integral membrane protein, porin [30]. Voltage-dependent anion channel (VDAC) is a major trafficking protein that forms a beta barrel spanning the outer membrane, which transports nucleotides, ions and metabolites between cytosol and intermembrane space [31, 32]. The IMM is found inside of the OMM, which encloses mitochondrial matrix, extensively folded and compartmentalized [33]. The IMM is non-permeable to nucleotides, sugars and small ions; thus specific carrier proteins enable the molecules to transport across the membrane [34].

The mitochondrial respiratory complexes I–IV, in which electrochemical gradient is generated for OXPHOS to occur for ATP synthesis, are embedded in the IMM [22]. Mitochondria contain two aqueous compartments: the IMS and matrix. The IMS, existing between the OMM and IMM, relays molecular transport from cytosol to mitochondrial matrix or reversely [35]. The compositions of small molecules such as ions and sugars in IMS are chemically similar to those in cytosol, as OMM is selectively permeable to those molecules [36]. However, in case of large proteins, the specific signalling peptides are required to be transported across the OMM. Thus, the protein composition of the IMS is different to the protein composition of the cytosol (e.g. cytochrome c) [37]. The mitochondrial matrix, enclosed by IMM, contains mitochondrial DNA (mtDNA), RNA and proteins. Especially, a number of proteins in the matrix are involved in diverse biochemical processes such as tricarboxylic acid (TCA) cycle, fatty acid oxidation, amino acid degradation and mitochondrial dynamics (fission and fusion) [27, 38] (**Figure 1**).
