ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1.
Melanosomes are lysosome-related organelles that serve as specialized sites of melanin synthesis and storage in melanocytes. The progression of melanosomes through the different stages of their formation requires trafficking of specific proteins and membrane constituents in a sequential manner, whic...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0075313 |
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| author | Eyal Kalie Minoo Razi Sharon A Tooze |
| author_facet | Eyal Kalie Minoo Razi Sharon A Tooze |
| author_sort | Eyal Kalie |
| collection | DOAJ |
| description | Melanosomes are lysosome-related organelles that serve as specialized sites of melanin synthesis and storage in melanocytes. The progression of melanosomes through the different stages of their formation requires trafficking of specific proteins and membrane constituents in a sequential manner, which is likely to deploy ubiquitous cellular machinery along with melanocyte-specific proteins. Recent evidence revealed a connection between melanogenesis and the autophagy machinery, suggesting a novel role for members of the latter in melanocytes. Here we focused on ULK1, a key autophagy protein which is negatively regulated by mTORC1, to assess its potential role in melanogenesis in MNT-1 cells. We found that ULK1 depletion causes an increase in melanin levels, suggesting an inhibitory function for this protein in melanogenesis. Furthermore, this increase was accompanied by increased transcription of MITF (microphthalmia-associated transcription factor) and tyrosinase and by elevated protein levels of tyrosinase, the rate-limiting factor in melanin biogenesis. We also provide evidence to show that ULK1 function in this context is independent of the canonical ULK1 autophagy partners, ATG13 and FIP200. Furthermore we show that regulation of melanogenesis by ULK1 is independent of mTORC1 inhibition. Our data thus provide intriguing insights regarding the involvement of the key regulatory autophagy machinery in melanogenesis. |
| format | Article |
| id | doaj-art-80f31be03f8a4c718d4da9de62cfd9d5 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-80f31be03f8a4c718d4da9de62cfd9d52025-08-20T03:46:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7531310.1371/journal.pone.0075313ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1.Eyal KalieMinoo RaziSharon A ToozeMelanosomes are lysosome-related organelles that serve as specialized sites of melanin synthesis and storage in melanocytes. The progression of melanosomes through the different stages of their formation requires trafficking of specific proteins and membrane constituents in a sequential manner, which is likely to deploy ubiquitous cellular machinery along with melanocyte-specific proteins. Recent evidence revealed a connection between melanogenesis and the autophagy machinery, suggesting a novel role for members of the latter in melanocytes. Here we focused on ULK1, a key autophagy protein which is negatively regulated by mTORC1, to assess its potential role in melanogenesis in MNT-1 cells. We found that ULK1 depletion causes an increase in melanin levels, suggesting an inhibitory function for this protein in melanogenesis. Furthermore, this increase was accompanied by increased transcription of MITF (microphthalmia-associated transcription factor) and tyrosinase and by elevated protein levels of tyrosinase, the rate-limiting factor in melanin biogenesis. We also provide evidence to show that ULK1 function in this context is independent of the canonical ULK1 autophagy partners, ATG13 and FIP200. Furthermore we show that regulation of melanogenesis by ULK1 is independent of mTORC1 inhibition. Our data thus provide intriguing insights regarding the involvement of the key regulatory autophagy machinery in melanogenesis.https://doi.org/10.1371/journal.pone.0075313 |
| spellingShingle | Eyal Kalie Minoo Razi Sharon A Tooze ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. PLoS ONE |
| title | ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. |
| title_full | ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. |
| title_fullStr | ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. |
| title_full_unstemmed | ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. |
| title_short | ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. |
| title_sort | ulk1 regulates melanin levels in mnt 1 cells independently of mtorc1 |
| url | https://doi.org/10.1371/journal.pone.0075313 |
| work_keys_str_mv | AT eyalkalie ulk1regulatesmelaninlevelsinmnt1cellsindependentlyofmtorc1 AT minoorazi ulk1regulatesmelaninlevelsinmnt1cellsindependentlyofmtorc1 AT sharonatooze ulk1regulatesmelaninlevelsinmnt1cellsindependentlyofmtorc1 |