Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator.
Therapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating cutaneous hyperpigmentary conditions. Towards defining new potential targets, we followed temporal dynamics of melanogenesis using a cell-autonomous pigmentation model. Our study...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-05-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3001634 |
| _version_ | 1797831684205314048 |
|---|---|
| author | Farina Sultan Reelina Basu Divya Murthy Manisha Kochar Kuldeep S Attri Ayush Aggarwal Pooja Kumari Pooja Dnyane Jyoti Tanwar Rajender K Motiani Archana Singh Chetan Gadgil Neel Sarovar Bhavesh Pankaj K Singh Vivek T Natarajan Rajesh S Gokhale |
| author_facet | Farina Sultan Reelina Basu Divya Murthy Manisha Kochar Kuldeep S Attri Ayush Aggarwal Pooja Kumari Pooja Dnyane Jyoti Tanwar Rajender K Motiani Archana Singh Chetan Gadgil Neel Sarovar Bhavesh Pankaj K Singh Vivek T Natarajan Rajesh S Gokhale |
| author_sort | Farina Sultan |
| collection | DOAJ |
| description | Therapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating cutaneous hyperpigmentary conditions. Towards defining new potential targets, we followed temporal dynamics of melanogenesis using a cell-autonomous pigmentation model. Our study elucidates 3 dominant phases of synchronized metabolic and transcriptional reprogramming. The melanogenic trigger is associated with high MITF levels along with rapid uptake of glucose. The transition to pigmented state is accompanied by increased glucose channelisation to anabolic pathways that support melanosome biogenesis. SREBF1-mediated up-regulation of fatty acid synthesis results in a transient accumulation of lipid droplets and enhancement of fatty acids oxidation through mitochondrial respiration. While this heightened bioenergetic activity is important to sustain melanogenesis, it impairs mitochondria lately, shifting the metabolism towards glycolysis. This recovery phase is accompanied by activation of the NRF2 detoxication pathway. Finally, we show that inhibitors of lipid metabolism can resolve hyperpigmentary conditions in a guinea pig UV-tanning model. Our study reveals rewiring of the metabolic circuit during melanogenesis, and fatty acid metabolism as a potential therapeutic target in a variety of cutaneous diseases manifesting hyperpigmentary phenotype. |
| first_indexed | 2024-04-09T13:55:45Z |
| format | Article |
| id | doaj.art-6e9086293249493e8277110524afd0a3 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-09T13:55:45Z |
| publishDate | 2022-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-6e9086293249493e8277110524afd0a32023-05-08T05:30:31ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-05-01205e300163410.1371/journal.pbio.3001634Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator.Farina SultanReelina BasuDivya MurthyManisha KocharKuldeep S AttriAyush AggarwalPooja KumariPooja DnyaneJyoti TanwarRajender K MotianiArchana SinghChetan GadgilNeel Sarovar BhaveshPankaj K SinghVivek T NatarajanRajesh S GokhaleTherapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating cutaneous hyperpigmentary conditions. Towards defining new potential targets, we followed temporal dynamics of melanogenesis using a cell-autonomous pigmentation model. Our study elucidates 3 dominant phases of synchronized metabolic and transcriptional reprogramming. The melanogenic trigger is associated with high MITF levels along with rapid uptake of glucose. The transition to pigmented state is accompanied by increased glucose channelisation to anabolic pathways that support melanosome biogenesis. SREBF1-mediated up-regulation of fatty acid synthesis results in a transient accumulation of lipid droplets and enhancement of fatty acids oxidation through mitochondrial respiration. While this heightened bioenergetic activity is important to sustain melanogenesis, it impairs mitochondria lately, shifting the metabolism towards glycolysis. This recovery phase is accompanied by activation of the NRF2 detoxication pathway. Finally, we show that inhibitors of lipid metabolism can resolve hyperpigmentary conditions in a guinea pig UV-tanning model. Our study reveals rewiring of the metabolic circuit during melanogenesis, and fatty acid metabolism as a potential therapeutic target in a variety of cutaneous diseases manifesting hyperpigmentary phenotype.https://doi.org/10.1371/journal.pbio.3001634 |
| spellingShingle | Farina Sultan Reelina Basu Divya Murthy Manisha Kochar Kuldeep S Attri Ayush Aggarwal Pooja Kumari Pooja Dnyane Jyoti Tanwar Rajender K Motiani Archana Singh Chetan Gadgil Neel Sarovar Bhavesh Pankaj K Singh Vivek T Natarajan Rajesh S Gokhale Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator. PLoS Biology |
| title | Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator. |
| title_full | Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator. |
| title_fullStr | Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator. |
| title_full_unstemmed | Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator. |
| title_short | Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator. |
| title_sort | temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator |
| url | https://doi.org/10.1371/journal.pbio.3001634 |
| work_keys_str_mv | AT farinasultan temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT reelinabasu temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT divyamurthy temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT manishakochar temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT kuldeepsattri temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT ayushaggarwal temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT poojakumari temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT poojadnyane temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT jyotitanwar temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT rajenderkmotiani temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT archanasingh temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT chetangadgil temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT neelsarovarbhavesh temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT pankajksingh temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT vivektnatarajan temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator AT rajeshsgokhale temporalanalysisofmelanogenesisidentifiesfattyacidmetabolismaskeyskinpigmentregulator |