In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 5 ( 2022-5-18), p. e3001634-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001634
DOI:
10.1371/journal.pbio.3001634.g001
DOI:
10.1371/journal.pbio.3001634.g002
DOI:
10.1371/journal.pbio.3001634.g003
DOI:
10.1371/journal.pbio.3001634.g004
DOI:
10.1371/journal.pbio.3001634.g005
DOI:
10.1371/journal.pbio.3001634.g006
DOI:
10.1371/journal.pbio.3001634.g007
DOI:
10.1371/journal.pbio.3001634.t001
DOI:
10.1371/journal.pbio.3001634.t002
DOI:
10.1371/journal.pbio.3001634.s001
DOI:
10.1371/journal.pbio.3001634.s002
DOI:
10.1371/journal.pbio.3001634.s003
DOI:
10.1371/journal.pbio.3001634.s004
DOI:
10.1371/journal.pbio.3001634.s005
DOI:
10.1371/journal.pbio.3001634.s006
DOI:
10.1371/journal.pbio.3001634.s007
DOI:
10.1371/journal.pbio.3001634.s008
DOI:
10.1371/journal.pbio.3001634.s009
DOI:
10.1371/journal.pbio.3001634.s010
DOI:
10.1371/journal.pbio.3001634.s011
DOI:
10.1371/journal.pbio.3001634.s012
DOI:
10.1371/journal.pbio.3001634.s013
DOI:
10.1371/journal.pbio.3001634.s014
DOI:
10.1371/journal.pbio.3001634.s015
DOI:
10.1371/journal.pbio.3001634.s016
DOI:
10.1371/journal.pbio.3001634.r001
DOI:
10.1371/journal.pbio.3001634.r002
DOI:
10.1371/journal.pbio.3001634.r003
DOI:
10.1371/journal.pbio.3001634.r004
DOI:
10.1371/journal.pbio.3001634.r005
DOI:
10.1371/journal.pbio.3001634.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2126773-X
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