Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes

Ji Young Kim; Jihee Kim; Yuri Ahn; Eun Jung Lee; Shinwon Hwang; Abdurrahman Almurayshid; Keedon Park; Hwa Jee Chung; Heung Jae Kim; Si Hyung Lee; Myung Shik Lee; Sang Ho Oh

doi:10.1111/pcmr.12838

Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes

Ji Young Kim, Jihee Kim, Yuri Ahn, Eun Jung Lee, Shinwon Hwang, Abdurrahman Almurayshid, Keedon Park, Hwa Jee Chung, Heung Jae Kim, Si Hyung Lee, Myung Shik Lee, Sang Ho Oh

Department of Dermatology

Research output: Contribution to journal › Article › peer-review

47 Citations (Scopus)

Abstract

Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD-12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD-12-induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.

Original language	English
Pages (from-to)	403-415
Number of pages	13
Journal	Pigment Cell and Melanoma Research
Volume	33
Issue number	3
DOIs	https://doi.org/10.1111/pcmr.12838
Publication status	Published - 2020 May 1

Bibliographical note

Funding Information:
The authors thank Dr. Tamotsu Yoshimori for kind provision of the mRFP‐eGFP‐LC3 construct. We are grateful to Dr. Vincent Hearing (Pigment Cell Biology Section, NIH, USA) for providing MNT‐1 cells. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2016R1C1B2008015) and the Ministry of SMEs and Startups (Grill et al.), Korea, under the “Regional Specialized Industry Development Program (R&D, R0004413)” supervised by the Korea Institute for Advancement of Technology (KIAT).

Funding Information:
The authors thank Dr. Tamotsu Yoshimori for kind provision of the mRFP-eGFP-LC3 construct. We are grateful to Dr. Vincent Hearing (Pigment Cell Biology Section, NIH, USA) for providing MNT-1 cells. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2016R1C1B2008015) and the Ministry of SMEs and Startups (Grill et al.), Korea, under the ?Regional Specialized Industry Development Program (R&D, R0004413)? supervised by the Korea Institute for Advancement of Technology (KIAT).

Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)
Dermatology
Oncology

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10.1111/pcmr.12838

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@article{bad2d8306ffb409397dcecb0033ad143,

title = "Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes",

abstract = "Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD-12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD-12-induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.",

author = "Kim, {Ji Young} and Jihee Kim and Yuri Ahn and Lee, {Eun Jung} and Shinwon Hwang and Abdurrahman Almurayshid and Keedon Park and Chung, {Hwa Jee} and Kim, {Heung Jae} and Lee, {Si Hyung} and Lee, {Myung Shik} and Oh, {Sang Ho}",

note = "Funding Information: The authors thank Dr. Tamotsu Yoshimori for kind provision of the mRFP‐eGFP‐LC3 construct. We are grateful to Dr. Vincent Hearing (Pigment Cell Biology Section, NIH, USA) for providing MNT‐1 cells. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2016R1C1B2008015) and the Ministry of SMEs and Startups (Grill et al.), Korea, under the “Regional Specialized Industry Development Program (R&D, R0004413)” supervised by the Korea Institute for Advancement of Technology (KIAT). Funding Information: The authors thank Dr. Tamotsu Yoshimori for kind provision of the mRFP-eGFP-LC3 construct. We are grateful to Dr. Vincent Hearing (Pigment Cell Biology Section, NIH, USA) for providing MNT-1 cells. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2016R1C1B2008015) and the Ministry of SMEs and Startups (Grill et al.), Korea, under the ?Regional Specialized Industry Development Program (R&D, R0004413)? supervised by the Korea Institute for Advancement of Technology (KIAT). Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",

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T1 - Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes

AU - Kim, Ji Young

AU - Kim, Jihee

AU - Ahn, Yuri

AU - Lee, Eun Jung

AU - Hwang, Shinwon

AU - Almurayshid, Abdurrahman

AU - Park, Keedon

AU - Chung, Hwa Jee

AU - Kim, Heung Jae

AU - Lee, Si Hyung

AU - Lee, Myung Shik

AU - Oh, Sang Ho

N1 - Funding Information: The authors thank Dr. Tamotsu Yoshimori for kind provision of the mRFP‐eGFP‐LC3 construct. We are grateful to Dr. Vincent Hearing (Pigment Cell Biology Section, NIH, USA) for providing MNT‐1 cells. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2016R1C1B2008015) and the Ministry of SMEs and Startups (Grill et al.), Korea, under the “Regional Specialized Industry Development Program (R&D, R0004413)” supervised by the Korea Institute for Advancement of Technology (KIAT). Funding Information: The authors thank Dr. Tamotsu Yoshimori for kind provision of the mRFP-eGFP-LC3 construct. We are grateful to Dr. Vincent Hearing (Pigment Cell Biology Section, NIH, USA) for providing MNT-1 cells. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2016R1C1B2008015) and the Ministry of SMEs and Startups (Grill et al.), Korea, under the ?Regional Specialized Industry Development Program (R&D, R0004413)? supervised by the Korea Institute for Advancement of Technology (KIAT). Publisher Copyright: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

PY - 2020/5/1

Y1 - 2020/5/1

N2 - Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD-12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD-12-induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.

AB - Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD-12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD-12-induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.

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Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes

Abstract

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