Cell death process of outermost epidermal layer is elucidated

April 20, 2021

Intracellular acidification is essential for normal formation of the stratum corneum

A joint research group of RIKEN, Keio University, the National Institute for Physiological Sciences, the Exploratory Research Center on Life and Living Systems, and the Japan Agency for Medical Research and Development elucidated the process of the death of skin epidermal cells, and proposed a new type of cell death, "corneoptosis".

In cells of the epidermis, the nuclei and mitochondria essential for the cells to survive are abolished (cell death), and the stratum corneum (SC), the outermost epidermal layer of the skin, is formed from the remnants of the dead cells. However, the mechanism of how nuclei and mitochondria vanish has remained unknown.

The joint research group independently developed a live imaging method and examined the epidermis of live mice. They found that, in the process of death of stratum granulosum cells below the stratum corneum, elevation in the concentration of calcium ions (Ca2+) continued for an hour followed by intracellular acidification with the Ca2+ level remained high. Without this acidification, the nuclei would not disappear, which leads to production of abnormal corneocytes. In addition, they found that the temperature-sensitive calcium channel, TRPV3 protein, regulates the timing of acidification.

The results of this study will help elucidate pathogenic mechanisms of allergic diseases such as atopic dermatitis which is known to be attributed to skin barrier disfunction of the stratum corneum, the uppermost layer of the skin.

Original article
Proceedings of the National Academy of Sciences of the United States of America doi:10.1073/pnas.2020722118
T. Matsui, N. Kadono-Maekubo, Y. Suzuki, Y. Furuichi, K. Shiraga, H. Sasaki, A. Ishida, S. Sonoko Takahashi, T. Okada, K. Toyooka, J. Sharif, T. Abe, H. Kiyonari, M. Tominaga, A. Miyawaki, M. Amagai,
"A unique mode of keratinocyte death requires intracellular acidification".
Kiminori Toyooka
Senior Technical Scientist
Mass Spectrometry and Microscopy Unit