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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Main Authors: Eyal Kalie, Minoo Razi, Sharon A Tooze
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
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.
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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