Topical Inhibition of the Electron Transport Chain Can Stimulate the Hair Cycle

Matilde Miranda; Heather Christofk; D Leanne Jones; William E Lowry

doi:10.1016/j.jid.2017.10.021

Topical Inhibition of the Electron Transport Chain Can Stimulate the Hair Cycle

J Invest Dermatol. 2018 Apr;138(4):968-972. doi: 10.1016/j.jid.2017.10.021. Epub 2017 Oct 26.

Authors

Matilde Miranda¹, Heather Christofk², D Leanne Jones³, William E Lowry⁴

Affiliations

¹ Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, USA; Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA.
² Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, USA; Eli and Edythe Broad Center for Regenerative Medicine, University of California Los Angeles, Los Angeles, California, USA.
³ Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, USA; Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA; Eli and Edythe Broad Center for Regenerative Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁴ Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, USA; Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA; Eli and Edythe Broad Center for Regenerative Medicine, University of California Los Angeles, Los Angeles, California, USA. Electronic address: blowry@ucla.edu.

Abstract

While many signaling pathways have been implicated in control of activation of adult hair follicle stem cells and the hair cycle, less is known about cell intrinsic mechanisms of stem cell control. We previously identified lactate production as a key cell intrinsic regulator of hair follicle stem cell activity, suggesting that cellular metabolism is important in stem cell activation. Others have used transgenic methods to suggest that transgenic blockade of the Electron Transport Chain (ETC) leads to degeneration of the hair follicle. Here, we show that pharmacological abrogation of ETC activity, as opposed to complete ablation of ETC, can promote hair cycle activation without significant cell toxicity. Furthermore, metabolic data suggest that ETC inhibition leads to increased pyruvate accessibility for the Ldh enzyme and therefore increased lactate production, which we previously showed can promote hair cycle activation. Finally, this type of ETC inhibition can even be used to accelerate the hair cycle in aged mice. These results point toward an unexpected and safe method to promote hair follicle stem cell activation.

Publication types

Letter
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Topical
Animals
Animals, Newborn
Cells, Cultured
Electron Transport
Electron Transport Chain Complex Proteins / drug effects
Electron Transport Chain Complex Proteins / metabolism*
Hair Follicle / cytology
Hair Follicle / diagnostic imaging*
Hair Follicle / drug effects
Models, Animal
Phenformin / administration & dosage*

Substances

Electron Transport Chain Complex Proteins
Phenformin

Abstract

Publication types

MeSH terms

Substances

Grants and funding