A role for human mitochondrial complex II in the production of reactive oxygen species in human skin

Abstract

The mitochondrial respiratory chain is a major generator of cellular oxidative stress, thought to be an underlying cause of the carcinogenic and ageing process in many tissues including skin. Previous studies of the relative contributions of the respiratory chain (RC) complexes I, II and III towards production of reactive oxygen species (ROS) have focussed on rat tissues and certainly not on human skin which is surprising as this tissue is regularly exposed to UVA in sunlight, a potent generator of cellular oxidative stress. In a novel approach we have used an array of established specific metabolic inhibitors and DHR123 fluorescence to study the relative roles of the mitochondrial RC complexes in cellular ROS production in 2 types of human skin cells. These include additional enhancement of ROS production by exposure to physiological levels of UVA. The effects within epidermal and dermal derived skin cells are compared to other tissue cell types as well as those harbouring a compromised mitochondrial status (Rho-zero A549). The results show that the complex II inhibitor, TTFA, was the only RC inhibitor to significantly increase UVA-induced ROS production in both skin cell types (P<0.05) suggesting that the role of human skin complex II in terms of influencing ROS production is more important than previously thought particularly in comparison to liver cells. Interestingly, two-fold greater maximal activity of complex II enzyme was observed in both skin cell types compared to liver (P<0.001). The activities of RC enzymes appear to decrease with increasing age and telomere length is correlated with ageing. Our study showed that the level of maximal complex II activity was higher in the MRC5/hTERT (human lung fibroblasts transfected with telomerase) cells than the corresponding wild type cells (P=0.0012) which can be considered (in terms of telomerase activity) as models of younger and older cells respectively.

Determination of the Action Spectrum of UVR-Induced Mitochondrial DNA Damage in Human Skin Cells

“…There is an established link between ROS production, mtDNA damage and skin ageing (Anderson et al, 2014). These new data clearly support the continued need for systems to manage sun exposure (including appropriate clothing, behaviour and sunscreens).…”

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

“…The current study suggests that T 4 , an inexpensive, toxicologically very well-defined hormone that has been systemically administered in clinical medicine for decades (Biondi and Wartofsky, 2014;Topliss and Soh, 2013) and is intracutaneously deiodinated to T 3 (van Beek et al, 2008), could serve in the treatment of skin conditions and pathologies connected with a decline in mitochondrial function (Boulton et al, 2015), intrinsic and extrinsic skin aging (Anderson et al, 2014; M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 7 Berneburg, 2008;Gilchrest, 2013;Glass et al, 2013;Grillon et al, 2012;Kaneko et al, 2012;Oyewole et al, 2014). Topical application of T 4 is expected to reduce the well-known adverse effects associated with elevated systemic TH levels (Kharlip and Cooper, 2009;Taylor et al, 2013;Walrand et al, 2014).…”

Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation

“…Intrinsic or chronological aging is the unavoidable occurrence that includes several influences like genetics, metabolism, and the passage of time, where repair functions become slow or defective [2,13,[18][19][20][21]. For example, in intrinsic aging, there is ROS production via normal oxidative metabolism within cells that is inevitable, but contributes in a modest way to skin aging compared to extrinsic aging [2,18,19]. Extrinsic aging comes from external sources that increase oxidative stress, which include sunlight, especially ultraviolet radiation (UVR), temperature conditions, like cold weather, and air/water pollution.…”