A role for human mitochondrial complex II in the production of reactive oxygen species in human skin
Open accessAbstract
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.
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Intrinsic aging includes ROS production via normal oxidative metabolism within cells that is inevitable, but contributes modestly to skin aging compared to extrinsic aging.
“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].”
Unlike nuclear DNA (nDNA), multiple copies of mitochondrial DNA (mtDNA) exist within each cell and are found in close proximity to the electron transport chain (ETC) making them extremely vulnerable to the effects of oxidative stress, exacerbated further by the fact that mtDNA has limited repair mechanisms.
“Unlike nuclear DNA (nDNA), multiple copies of mitochondrial DNA (mtDNA) exist within each cell and are found in close proximity to the electron transport chain (ETC) making them extremely vulnerable to the effects of oxidative stress, exacerbated further by the fact that mtDNA has limited repair mechanisms [Anderson et al., 2014].”
From Oxidative stress and ageing (2016) · cites this paper as Anderson et al., 2014
More recently complex II has been shown to be implicated in human dermal fibroblast senescence and ageing.
“More recently complex II has been shown to be implicated in human dermal fibroblast senescence and ageing [Anderson et al., 2014; Bowman and Birch-Machin, 2016; Boulton and Birch-Machin 2015].”
From Oxidative stress and ageing (2016) · cites this paper as Anderson et al., 2014
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References 50 · Cited by 65
Research works printed but not linked: 1
- [30]Scheffler I. Mitochondria second edition 2008 John Wiley and Sons Hoboken, NJ
- Authors
- Anderson, A., Bowman, A., Boulton, S. J., Manning, P., & Birch-Machin, M. A.
- Affiliations
- Newcastle University (GB)
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2014
- Volume
- 2
- Pages
- 1016-1022
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC4215388
- OpenAlex
- W2127264357
- Cited by
- 65
- References
- 50
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 4 · 2014: 2
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Medical Research Council
- Institute of Cellular Medicine
- Newcastle University (C0241N3010)
- North Eastern Skin Research Fund (RES/0241/7536)
- National Institute for Health Research Newcastle Biomedical Research Centre (BH120752)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- succinate dehydrogenase, reactive oxygen species, skin, UVA, oxidative stress, electron transport chain, epidermal cells, dermal cells, telomerase, telomere length, skin aging, respiratory chain inhibitors
- MeSH terms
- Cell Line, Humans, Mitochondria, Skin, Ultraviolet Rays, Reactive Oxygen Species, Mitochondrial Proteins, Electron Transport Complex II
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