Targeting mitochondria in dermatological therapy: beyond oxidative damage and skin aging

Tongyu C. Wikramanayake, Jérémy Chéret, Alec Sevilla, Mark Birch-Machin, Ralf Paus

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: The analysis of the role of the mitochondria in oxidative damage and skin aging has been a significant aspect of dermatological research. Mitochondria generate most reactive oxygen species (ROS) which, in excess, are cytotoxic and DNA-damaging and promote (photo-)aging. However, ROS also possesses key physiological and regulatory functions and mitochondrial dysfunction is prominent in several not primarily senescence-associated skin diseases and skin cancers. Although many standard dermatotherapeutics modulate mitochondrial function, dermatological therapy rarely targets the mitochondria. Accordingly, there is a rationale for ‘mitochondrial dermatology’-based approaches to be applied to therapeutic research, as we advocate here. Areas covered: This paper examines the functions of mitochondria in cutaneous physiology beyond energy (ATP) and ROS production. Keratinocyte differentiation and epidermal barrier maintenance, appendage morphogenesis and homeostasis, photoaging and skin cancer are considered. Based on related PubMed search results, the paper evaluates thyroid hormones, glucocorticoids, Vitamin D3 derivatives, retinoids, cannabinoid receptor agonists, PPARγ agonists, thyrotropin, and thyrotropin-releasing hormone as instructive lead compounds. Moreover, the mitochondrial protein MPZL3 as a promising new drug target for future ‘mitochondrial dermatology’ is highlighted. Expert opinion: Future dermatological therapeutic research should have a mitochondrial medicine emphasis. Focusing on selected lead agents, protein targets, in silico drug design, and model diseases will fertilize a mito-centric approach.

Original languageEnglish (US)
Pages (from-to)233-259
Number of pages27
JournalExpert Opinion on Therapeutic Targets
Volume26
Issue number3
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • Reactive oxygen species (ROS)
  • alopecia
  • appendage
  • epidermis
  • hair follicle
  • mitochondria
  • myelin protein zero-like 3 (MPZL3)
  • sebaceous gland
  • skin cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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