**1. Introduction**

Mitochondria are double-membrane-bound cellular organelles found in most eukaryotic organisms. The number of mitochondria in cell differs widely according to organisms, tissues and cell types, which is determined by the energy demand. Mitochondria occupy around 40% of the cytoplasm in heart muscle cells and 20–25% with ~2000 per cell in liver cells. Mitochondria, as the power plants of the cell, mainly generate energy in forms of adenosine triphosphates (ATPs) by oxidative phosphorylation (OXPHOS) during glucose metabolism [1, 2]. The OXPHOS is coupled with mitochondrial respiration in which mitochondrial transmembrane potential (MMP, ΔΨm) is generated by pumping the protons via mitochondrial complexes I, III and IV of the electron transport chain (ETC) [3].

Molecular oxygen (O2) is essential for the mitochondrial bioenergetic metabolism, which functions as the final electron acceptor for cytochrome *c* oxidase (complex IV) in the respiratory ETC that catalyses the four-electron reduction of O2 to H2O. Mitochondria are an important source of reactive oxygen species (ROS) within most mammalian cells [4, 5]; mitochondrial ROS (mROS) are basically produced as byproducts of this bioenergetic metabolism during the OXPHOS [6]. Electron leaks at complex I and III from ETC lead to forming partially reduced and highly

reactive metabolites of O2, including superoxide anion (O2 ·<sup>−</sup>) and hydrogen peroxide (H2O2), formed by one- and two-electron reductions of O2, respectively [7]. In the presence of transition metal ions, the more reactive hydroxyl radical (OH· ) is formed. The O2 ·<sup>−</sup> is rapidly dismutated to H2O2 by two dismutases including Cu/ Zn-superoxide dismutase (Cu/ZnSOD) in mitochondrial intermembrane space and manganese-dependent superoxide dismutase (MnSOD) in mitochondrial matrix. Unless the dismutation of O2 ·<sup>−</sup> is catalyzed into H2O2, the radical oxidant promotes DNA damage, protein oxidation and lipid peroxidation in many types of cells. H2O2 is also cell damaging molecule to be degraded to water by catalase [8]. Although the O2 ·<sup>−</sup> generation by respiratory complexes is a well-established phenomenon, it is still poorly understood in mechanism [9].

Mitochondria have been implicated in the regulation of a number of physiological and pathological processes, including proliferation, differentiation, programmed cell death, innate immunity, autophagy, redox signalling, calcium homeostasis, hypoxic stress responses and stem cell reprogramming [10–16]. The mROS production contributes to mitochondrial damage in a range of pathologies, which is also is closely related to redox signalling in the cell [4, 17]. However, accumulating evidences show that mROS are not only deleterious molecules derived from the cellular metabolism but also indispensable participants in diverse cellular signalling and regulations [18–20].

In this chapter, we briefly summarize recent developments in our understanding of the involvement of mROS as signalling mediators in redox biology, rather than pathological stress, underlying physiological conditions.
