Stressed out mitochondria: the role of mitochondria in ageing and cancer focussing on strategies and opportunities in human skin

Abstract

Mitochondrial DNA damage has been used as a successful and unique biomarker of tissue stress. A valuable example of this is sun damage in human skin which leads to ageing and skin cancer. The skin is constantly exposed to the harmful effects of sunlight, such as ultraviolet radiation, which causes it to age with observable characteristic features as well as clinical precancerous lesions and skin cancer. Formation of free radicals by the sun's harmful rays which contribute to oxidative stress has been linked to the induction of deletions and mutations in the mitochondrial DNA. These markers of mitochondrial DNA damage have been proposed to contribute to the mechanisms of ageing in many tissues including skin and are associated with many diseases including cancer. In this article we highlight the role of this important organelle in ageing and cancer with particular emphasis on experimental strategies in the skin.

Keywords: 8-OHdG; 8-hydroxydeoxyguanosine; ADP; ATP; CPD; D-loop; DNA; EPR; ERK1/2; ETC; Electron transport chain; FADH(2); FOXO; FRTA; H(+); H(2)O(2); IRA; IRB; IRC; Infrared radiation; MED; MMP1; MMPs; Mitochondrial DNA; NADH; Nrf2; O(2); O(2)()(−); O(H); O(L); OH()(−); P(H); P(L); PCR; PI(3)K; RNA; ROS; Reactive oxygen species; SED; TTFA; UVA; UVB; UVC; UVR; Ultraviolet radiation; adenosine diphosphate; adenosine triphosphate; base pairs; bp; cyclobutane pyrimidine dimer; deoxyribonucleic acid; displacement loop; electron transport chain; electroparamagnetic resonance; extracellular signal-regulated kinase 1/2; forkhead box protein (a family of transcription factors); free radical theory of ageing; hydrogen peroxide; hydroxyl radical; infrared A radiation; infrared B radiation; infrared C radiation; matrix metalloproteinase 1; matrix metalloproteinases; minimal erythema dose; mitochondrial DNA; mtDNA; nuclear factor-like 2 (transcription factor); origin of heavy strand replication; origin of light strand replication; oxygen; phosphor-inositide 3-kinase; polymerase chain reaction; promoter for initiation of heavy strand transcription; promoter for initiation of light strand transcription; proton; reactive oxygen species; reduced flavin adenine dinucleotide; reduced nicotinamide adenine dinucleotide; ribonucleic acid; standard erythema dose; superoxide anion; thenoyl trifluoroacetate; ultraviolet A radiation wavelength 320–400nm; ultraviolet B radiation wavelength 280–320nm; ultraviolet C radiation wavelength 110–280nm; ultraviolet radiation.