## 2 Mitochondrial Reactive Oxygen Species  
Mitochondrial dysfunction and the generation of ROS have garnered increasing attention in the context of psoriasis pathogenesis. This review delves into the background of mitochondrial reactive oxygen species (mtROS) and their intricate relationship with psoriasis, shedding light on their potential as key drivers of disease progression. MtROS are a natural byproduct of cellular respiration that occurs in the mitochondria [5]. When oxidative phosphorylation produces adenosine triphosphate (ATP) as a source of energy, electrons from the electron transport chain escape and react with oxygen, generating ROS such as superoxide anion (O\({}_{2}\)\({}^{-}\)), hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), and hydroxyl radical (OH) [5; 7; 12]. While ROS are integral to cell signaling and immune response regulation, their excessive production or inadequate removal can result in oxidative stress [5]. Under physiological conditions, low levels of ROS serve as signaling molecules involved in various cellular processes, including proliferation, differentiation, and immune responses [2; 5]. However, excessive or dysregulated mtROS production can disrupt cellular homeostasis, leading to oxidative stress, DNA damage, and mitochondrial dysfunction [2; 5; 7]. Given mitochondria's crucial role in cellular metabolism and homeostasis, any imbalance in ROS production and antioxidant capacity due to factors like mitochondrial dysfunction, impaired antioxidant defenses, or environmental stressors can contribute to oxidative damage, implicating diseases such as psoriasis [3]. Psoriasis, characterized by persistent inflammation, abnormal keratinocyte proliferation, and immunological dysregulation, exemplifies an inflammatory condition where mitochondrial dysfunction and mtROS production may play pivotal roles [13]. Firstly, mtROS has been indicated by several studies that it is proven to promote inflammation in psoriasis. The excessive production of ROS can activate pro-inflammatory signaling pathways, such as nuclear factor kappa B (NF-kB) and mitogen-activated protein kinases (MAPKs), prompting the release of pro-inflammatory cytokines and chemokines, thereby perpetuating chronic inflammation in psoriatic skin [7; 14; 15]. Pro-inflammatory cytokineslike interleukin-17 (IL-17A) and tumor necrosis factor-alpha (TNF-\(\alpha\)) further stimulate mtROS formation in immune cells and keratinocytes, perpetuating a cycle of inflammation and oxidative stress, worsening disease symptoms [15]. Moreover, mtROS-mediated oxidative stress can promote aberrant keratinocyte proliferation and differentiation, contributing to epidermal hyperplasia and plaque formation in psoriatic skin. As the primary site of psoriatic lesions, the skin is subject to inflammatory stimuli and environmental stressors that impair mitochondrial activity and increase ROS production in keratinocytes [3]. The bidirectional relationship between mtROS and psoriasis involves inflammation and cellular dysfunction exacerbating mitochondrial dysfunction and ROS production. Additionally, ROS and mtROS-induced oxidative damage disrupt normal cellular processes, triggering apoptosis, which, while essential for maintaining tissue homeostasis, can contribute to tissue damage and inflammation, as observed in psoriatic lesions [16]. Oxidative stress, a hallmark feature of psoriasis, results from an imbalance between ROS production and antioxidant defense mechanisms. The generation of mtROS can overwhelm the cell's antioxidant capacity, hence intensifying oxidative damage in psoriatic skin [17]. This imbalance can occur due to several factors, including increased ROS production from activated immune cells, mitochondrial dysfunction, and decreased antioxidant levels or activity [17; 18]. Addressing this imbalance through therapeutic strategies aimed at restoring antioxidant defenses holds promise for managing psoriasis by reducing inflammation and oxidative damage.