Abstract
The melanosome is a specialized membrane-bound organelle that is involved in melanin synthesis, storage, and transportation. In contrast to melanosome biogenesis, the processes underlying melanosome degradation remain largely unknown. Autophagy is a process that promotes degradation of intracellular components’ cooperative process between autophagosomes and lysosomes, and its role for process of melanosome degradation remains unclear. Here, we assessed the regulation of autophagy and its contributions to depigmentation associated with Melasolv (3,4,5-trimethoxycinnamate thymol ester). B16F1 cells-treated with Melasolv suppressed the α-MSH-stimulated increase of melanin content and resulted in the activation of autophagy. However, introduction of bafilomycin A1 strongly suppressed melanosome degradation in Melasolv-treated cells. Furthermore, inhibition of autophagy by ATG5 resulted in significant suppression of Melasolv-mediated depigmentation in α-MSH-treated cells. Taken together, our results suggest that treatment with Melasolv inhibits skin pigmentation by promoting melanosome degradation via autophagy activation.
Highlights
Organelles are specialized intracellular structures that perform specific critical roles for cell function and survival; the number of organelles can be modulated in response to specific functional and environmental needs [1]
Consistent with the previous report, Melasolv efficiently suppressed melanogenesis in B16F1 cells, despite the strong melanogenic stimulus provided by α-melanocytestimulating hormone (α-MSH) (Fig 1)
Earlier studies have reported that transcription factor EB (TFEB), which was phosphorylated in response to inhibition of mammalian target of rapamycin, is retained in the cytoplasm, whereas dephosphorylated TFEB undergoes translocation to the nucleus to induce the transcription of autophagy-associated target genes including various autophagy-related genes (ATGs) [12]
Summary
Organelles are specialized intracellular structures that perform specific critical roles for cell function and survival; the number of organelles can be modulated in response to specific functional and environmental needs [1]. Autophagy is a pathway that promotes intracellular degradation of large protein aggregates and damaged organelles. During autophagy, targeted cytosolic constituents are isolated within double-membrane vesicles called autophagosomes; these eventually fuse with lysosomes and undergo degradation [2, 3]. The acidic pH in the lumens of these organelles is optimal for the activities of lysosomal hydrolytic enzymes that degrade cellular components [2, 3]. Recent studies have shown that target organelles can be eliminated via organelle-specific autophagy, for example, mitophagy, which is a unique pathway that promotes mitochondrial autophagy [4, 5]
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