How mitochondria record the effects of UV exposure and oxidative stress using human skin as a model tissue

Abstract

The accumulation of mitochondrial DNA (mtDNA) mutations has been proposed as an underlying cause of the ageing process and mutations have been associated with cancer in many tissues, including human skin. This involvement is linked to the key roles of mitochondrial function and mtDNA in oxidative stress production and as a mediator of apoptosis. We and others have pioneered the use of mtDNA damage as a highly sensitive biomarker of ultraviolet exposure in human skin and have also shown that the accumulation of an ageing-dependent mtDNA mutation is accelerated by exposure to sunlight, which is known to induce oxidative stress in skin. This is important as ultraviolet radiation (UVR)-induced gene mutations play a key role in the development of skin cancer and ageing in human skin. Novel applications of mtDNA as a biomarker of UVR-induced oxidative stress will also be highlighted in this review.

Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin

“…Both UVA and UVB have been shown to contribute to UVR-induced ageing; however, due to its ability to penetrate deeper into the dermis, UVA has been shown to cause disproportionately more damage [5]. Exposure of skin to UVR is known to stimulate the photochemical generation of ROS, which includes superoxide anions and hydrogen peroxide [6]. Although ROS are continuously produced in the skin and are involved in physiological processes, there is accumulating evidence for the harmful effects of high ROS concentrations following exposure to UVR [5].…”

“…Although ROS are continuously produced in the skin and are involved in physiological processes, there is accumulating evidence for the harmful effects of high ROS concentrations following exposure to UVR [5]. Antioxidants are produced by the skin to counteract the harmful effects of ROS; however, the higher concentrations of ROS generated following UVR exposure can induce an imbalance in cellular antioxidant defence systems, leading to oxidative stress [6]. UVB can also be directly absorbed by DNA, leading to direct induction of damage within cells.…”

“…Damage to mitochondrial DNA can lead to mitochondrial dysfunction which may subsequently increase the production of ROS. This leads to a continuing vicious cycle whereby the generation of ROS may lead to further mitochondrial DNA damage [6]. This is of particular importance as there is increasing evidence that alterations in mitochondrial function can adversely impact skin health and lead to skin disease [26].…”

“…Mitochondria are dynamic double-membrane-bound organelles found within the cytoplasm of eukaryotic cells. The primary function of mitochondria is the production of cellular energy, through a process termed oxidative phosphorylation, in the form of adenosine triphosphate (ATP) [6]. Oxygen metabolism in the mitochondria leads to the generation of reactive oxygen species (ROS).…”

Point Mutations, Their Transition Rates and Involvements in Human and Animal Disorders

“…According to this theory, mtDNA mutations caused by ROS accumulate within the cell, leading to impaired respiratory chain proteins, thereby generating more ROS, which in turn causes higher mtDNA mutation rates. Although there are data supporting a direct functional role of mtDNA in ageing and photoageing (Trifunovic et al, 2004;Birch-Machin & Swalwell, 2010), there is still considerable debate about the type of mtDNA associated with ageing. For example, the most frequently reported DNA region under assumption presents 4977-bp common deletion, but its significance is under debate (Thayer et al, 2003;Meissner et al, 2010).…”