Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with a high prevalence worldwide. AD is a complex disease in which epidermal barrier impairment is considered the pathologic cornerstone. Moreover, there is a consensus that abnormal epidermal barrier function is the driving force in the development of skin inflammation, which, in turn, further weakens the barrier and perpetuates a vicious pathological cycle. Defective epidermal barrier leads to sustained epidermal cell renewal. The latter condition creates energetic stress in epidermal cells because of the high energy-demand of cell proliferation. Thus, we hypothesized that mitochondria, as the cell’s major energy producers, were hyperactivated in AD skin. We found more mitochondria in the epidermis of AD patients when compared to healthy donors. Moreover, mitochondria activity was enhanced in primary keratinocytes isolated from AD skin when compared to healthy cells. In addition, we observed, in AD keratinocytes, an upregulation of the expression of MnSOD and CuSOD. This increase of detoxification enzymes remained insufficient to restore the cellular redox balance, because pro-oxidant molecules mainly accumulated in mitochondria isolated from AD keratinocytes. Generation of 3D organotypic cultures (HEEs) with patient and healthy control cells confirmed results obtained with primary cells. Moreover, treatment of HEEs with drugs targeting mitochondria and mitochondria-related oxidative stress ameliorated cellular and molecular abnormalities in AD HEEs, including expression of filaggrin and corneodesmosin. Thus, mitochondria might be novel therapeutic targets in AD.

Mitochondria: novel therapeutic targets in atopic dermatitis?