Loss of dynamin-related protein 1 (Drp1) does not affect epidermal development or UVB-induced apoptosis but does accelerate UVB-induced carcinogenesis

J Dermatol Sci. 2020 Aug;99(2):109-118. doi: 10.1016/j.jdermsci.2020.06.009. Epub 2020 Jun 26.


Background: Mitochondrial morphology is controlled by fission and fusion. Dynamin-related protein 1 (Drp1, dynamin-1-like protein (Dnml1)) regulates mitochondrial fission, which is associated with cell division and apoptosis. We previously reported that DRP1 is indispensable for cell growth in cutaneous squamous cell carcinoma. However, little is known about Drp1 in normal epidermis/keratinocytes.

Objectives: We investigated the function of Drp1 in normal epidermis/keratinocytes.

Methods: Epidermis-specific Drp1 knockout (EKO) mice were analyzed.

Results: Epidermal development in the EKO mice were indistinguishable from those in the wild-type (WT) mice. Ultrastructural analysis and immunohistochemistry revealed that the mitochondria of keratinocytes in the EKO mice were neither elongated nor constricted. Drp1 knockdown did not diminish the cell growth of normal human keratinocytes. Both in vivo and in vitro, UVB-induced apoptosis in the EKO epidermis and keratinocytes did not differ from that in the WT mice. In chronic UVB-irradiation, the loss of Drp1 sensitized the epidermis to the development of skin tumors. Clinically, DRP1 is expressed more highly in sun-exposed skin than in non-exposed skin in individuals under age 40, but not in those over age 60.

Conclusion: EKO mice demonstrate that Drp1 is dispensable for the development and apoptosis of the epidermis. Drp1 plays critical roles in malignant tumors; thus, the molecular machinery of mitochondrial dynamics involving Drp1 could be a novel therapeutic target for malignant keratinocytic lesions. On the other hand, the anti-tumorigenic role of Drp1 in chronic UVB-induced carcinogenesis need to be further investigated.

Keywords: Apoptosis; Drp1; Epidermis; Knockout; Mitochondria; Ultraviolet.

MeSH terms

  • Adult
  • Age Factors
  • Animals
  • Animals, Newborn
  • Apoptosis / radiation effects
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinogenesis / radiation effects
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line
  • Disease Models, Animal
  • Dynamins / genetics
  • Dynamins / metabolism*
  • Epidermis / growth & development
  • Epidermis / pathology*
  • Epidermis / radiation effects
  • Epidermis / ultrastructure
  • Female
  • Gene Expression Profiling
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / pathology
  • Keratinocytes / radiation effects
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Mitochondrial Dynamics / genetics
  • Mitochondrial Dynamics / radiation effects
  • Primary Cell Culture
  • Retrospective Studies
  • Skin Neoplasms / etiology
  • Skin Neoplasms / pathology*
  • Stem Cells
  • Ultraviolet Rays / adverse effects*


  • DNM1L protein, human
  • Dnm1l protein, mouse
  • Dynamins