Temporal resolution of melanogenesis determine fatty acid metabolism as key skin pigment regulator
Temporal resolution of melanogenesis determine fatty acid metabolism as key skin pigment regulator
Abstract Therapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating meta-inflammatory-triggered cutaneous conditions. Modulators of cAMP signalling of melanocyte have met with minimal clinical efficacy. Towards defining new potential targets, we followed temporal dynamics orchestrating melanocyte differentiation by using a cell-autonomous pigmentation model. Our study elucidates three dominant phases of synchronized metabolic and transcriptional reprogramming. The induction phase is concomitant with a paradoxical decrease in MITF levels, reduced proliferation, and increased anabolic metabolism mediated by AKT phosphorylation. The melanogenic phase shows rapid uptake of glucose and fatty acid, transiently forming lipid droplets through SREBF1-mediated regulation of fatty acid metabolism. This heightened bioenergetic activity impairs mitochondria and the recovery phase is marked by a shift to aerobic glycolysis and activation of the NRF2 detoxication pathway. Finally, we show that inhibitors of lipid metabolism indeed resolve hyper-pigmentary conditions in a guinea pig UV-tanning model. Our studies reveal metabolic control mechanisms of melanocytes that could govern the balance between differentiation and proliferation in a variety of cutaneous diseases.
Kumari Pooja、Singh Archana、Gadgil Chetan、Singh Pankaj K.、Sultan Farina、Murthy Divya、Kochar Manisha、Basu Reelina、Attri Kuldeep S.、Natarajan Vivek T.、Gokhale Rajesh S.、Dnyane Pooja、Aggrawal Ayush、Bhavesh Neel S.
International Centre for Genetic Engineering and BiotechnologyCSIR-Institute of Genomics and Integrative Biology||Academy of Scientific and Innovative ResearchCSIR-Institute of Genomics and Integrative Biology||Academy of Scientific and Innovative Research||CSIR-National Chemical LaboratoryEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical CenterCSIR-Institute of Genomics and Integrative Biology||Academy of Scientific and Innovative ResearchCSIR-Institute of Genomics and Integrative BiologyNational Institute of ImmunologyCSIR-Institute of Genomics and Integrative BiologyEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical CenterCSIR-Institute of Genomics and Integrative Biology||Academy of Scientific and Innovative ResearchNational Institute of ImmunologyAcademy of Scientific and Innovative Research||CSIR-National Chemical LaboratoryCSIR-Institute of Genomics and Integrative Biology||Academy of Scientific and Innovative ResearchInternational Centre for Genetic Engineering and Biotechnology
皮肤病学、性病学基础医学生物科学研究方法、生物科学研究技术
Kumari Pooja,Singh Archana,Gadgil Chetan,Singh Pankaj K.,Sultan Farina,Murthy Divya,Kochar Manisha,Basu Reelina,Attri Kuldeep S.,Natarajan Vivek T.,Gokhale Rajesh S.,Dnyane Pooja,Aggrawal Ayush,Bhavesh Neel S..Temporal resolution of melanogenesis determine fatty acid metabolism as key skin pigment regulator[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2021.04.06.438588.点此复制
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