ArticleAutophagy2025
Deciphering melanophagy: role of the PTK2-ITCH-MLANA-OPTN cascade on melanophagy in melanocytes.
Article in Autophagy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Moranoline-EnrichedInternational journal of molecular sciences · 2026Article
- MLANA is a potential prognostic biomarker and correlated with immune infiltration in skin cutaneous melanoma.Clinical and experimental medicine · 2026Article
- Regulation of pexophagy by a novel TBK1-MARCHF7-PXMP4-NBR1 axis in PEX1-depleted HeLa cells.Autophagy · 2026Article
- Emerging perspectives on the selective autophagy of melanosomes: melanophagy.Experimental & molecular medicine · 2025Review
- The emerging roles of autophagy in the homeostasis of lysosome-related organelles.Frontiers in cell and developmental biology · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
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Abstract
Melanosomes play a pivotal role in skin color and photoprotection. In contrast to the well-elucidated pathway of melanosome biogenesis, the process of melanosome degradation, referred to as melanophagy, is largely unexplored. Previously, we discovered that 3,4,5-trimethoxycinnamate thymol ester (TCTE) effectively inhibits skin pigmentation by activating melanophagy. In this study, we discovered a new regulatory signaling cascade that controls melanophagy in TCTE-treated melanocytes. ITCH (itchy E3 ubiquitin protein ligase) facilitates ubiquitination of the melanosome membrane protein MLANA (melan-A) during TCTE-induced melanophagy. This ubiquitinated MLANA is then recognized by an autophagy receptor protein, OPTN (optineurin). Additionally, a phospho-kinase antibody array revealed that TCTE activates PTK2 (protein tyrosine kinase 2), which phosphorylates ITCH, enhancing the ubiquitination of MLANA. Furthermore, inhibition of either PTK2 or ITCH disrupts the ubiquitination of MLANA and the MLANA-OPTN interaction in TCTE-treated cells. Taken together, our findings highlight the critical role of the PTK2-ITCH-MLANA-OPTN cascade in orchestrating melanophagy progression.
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Registered trials
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