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Background: Coenzyme Q 10 (CoQ 10 ), also known as ubiquinone-10, is an important molecule of the mitochondrial respiratory chain that acts as an electron carrier between complexes I, II, and III and additionally functions as an antioxidant. Due to its bioenergetic properties, CoQ 10 is of high interest for therapeutic and cosmetic use. This study aims to characterize the metabolic impact of CoQ 10 on primary human dermal fibroblasts (HDF) using fluorescence lifetime imaging microscopy (FLIM) and electron microscopy., Methods: FLIM of nicotinamide adenine dinucleotide (NADH) is a robust method to characterize cellular energy metabolism that also provides spatial information. Electron microscopy offers a way to characterize the ultrastructure of mitochondria and reveal features not visible in FLIM., Results: We reported a shift towards longer lifetimes of NADH in primary fibroblasts from ten different donors upon treatment with CoQ 10 , which indicates the stimulation of oxidative phosphorylation. This is confirmed by phasor-based metabolic pattern segmentation, which showed localization of longer NADH lifetimes in CoQ 10 -treated cells, indicating activated mitochondria in the cytoplasm. In addition, a complementary investigation of the mitochondrial ultrastructure using transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) tomography showed a reduction in stress granules in CoQ 10 -treated cells., Conclusions: Together, FLIM and electron microscopy (EM) imaging strongly imply that CoQ 10 stimulates cellular energy metabolism., (© 2024 The Author(s). Published by IMR Press.)

The decline of mitochondrial function throughout the lifespan is directly linked to the development of ageing phenotypes of the skin. Here, we assessed alterations in markers of epidermal mitochondrial energy metabolism as a function of skin age. Human skin samples from distinct anatomical regions were obtained during routine dermatological surgery from 21 young (27.6 ± 1.71 year) and 22 old (76.2 ± 1.73 year) donors. Sections of skin samples were analysed by immunohistochemistry for mitochondrial subunits of each electron transport chain complex (I-V)/oxidative phosphorylation (OXPHOS), as well as proteins serving as a marker of mitochondrial mass (VDAC1) and the regulation of DNA transcription (TFAM). Staining intensities of ATP5F1A (comprising complex V) and TFAM in the epidermis of older subjects were significantly decreased compared with younger donors. Moreover, these effects were independent of UV exposure of the stained skin section. Overall, we demonstrate that ageing is associated with reduced protein levels of complex V of the mitochondrial respiratory chain and TFAM. These alterations may impair essential mitochondrial functions, exacerbating the cutaneous ageing process., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Coenzyme Q 10 (CoQ 10 ) is an endogenous lipophilic quinone, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the aging process. In fact, coenzyme Q 10 synthesis is known to decrease with age in different tissues including skin. Moreover, synthesis can be inhibited by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins, that are widely used hypocholesterolemic drugs. They target a key enzymatic step along the mevalonate pathway, involved in the synthesis of both cholesterol and isoprenylated compounds including CoQ 10 .In the present study, we show that pharmacological CoQ 10 deprivation at concentrations of statins > 10000 nM triggers intracellular oxidative stress, mitochondrial dysfunction and generates cell death in human dermal fibroblasts (HDF). On the contrary, at lower statin concentrations, cells and mainly mitochondria, are able to partially adapt and prevent oxidative imbalance and overt mitochondrial toxicity. Importantly, our data demonstrate that CoQ 10 decrease promotes mitochondrial permeability transition and bioenergetic dysfunction leading to premature aging of human dermal fibroblasts in vitro .