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Updated: Jul 8, 2026
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Transient receptor potential mucolipin 1 circumvents oxidative stress in primary human melanocytes
1Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
Background:
Transient Receptor Potential Mucolipin 1 (TRPML1) serves as a pivotal reactive oxygen species (ROS) sensor in cells, which is implicated in the regulation of autophagy. However, its function in melanocyte autophagy under oxidative stress remains elusive.
Methods:
The expression and ion channel function of TRPML1 were investigated using immunofluorescence and calcium imaging in primary human melanocytes (MCs). After activating TRPML1 with MLSA1 (TRPML1 agonist), autophagy-related molecules were investigated via western blot. ROS level, apoptosis- and autophagy-related molecules were investigated after pretreatment with MLSA1. After interference with TRPML1 expression, mitochondrial structures were visualized by electron microscopy with hydrogen peroxide (H2O2）treatment.
Results:
TRPML1 was expressed and functionally active in primary human MCs, and its activation promotes elevated expression of LC3-II and reduced apoptosis and ROS levels under oxidative stress. TRPML1 downregulation caused mitochondrial swelling and disruption of cristae structures under oxidative stress in primary human MCs.
Conclusions:
TRPML1 might mediate lysosomal autophagy in primary human MCs under oxidative stress, participating in mechanisms that maintain the oxidative and antioxidant systems in balance.
Insights
Transient Receptor Potential Mucolipin 1 (TRPML1) activates autophagy in melanocytes, reducing oxidative stress and apoptosis. This ion channel plays a key role in maintaining cellular balance under challenging conditions.
Area of Science:
- Cell Biology
- Molecular Biology
- Dermatology
Background:
- Transient Receptor Potential Mucolipin 1 (TRPML1) is a reactive oxygen species (ROS) sensor involved in autophagy.
- Its role in melanocyte autophagy under oxidative stress is not well understood.
Purpose of the Study:
- To investigate the function of TRPML1 in primary human melanocytes (MCs) under oxidative stress.
- To determine TRPML1's role in regulating autophagy, ROS levels, and apoptosis in MCs.
Main Methods:
- TRPML1 expression and function were assessed using immunofluorescence and calcium imaging in primary human MCs.
- Autophagy markers, ROS levels, and apoptosis were analyzed after TRPML1 activation or downregulation.
- Mitochondrial morphology was examined using electron microscopy following hydrogen peroxide treatment.
Main Results:
- TRPML1 is expressed and functional in primary human MCs.
- TRPML1 activation increased LC3-II expression and decreased apoptosis and ROS levels under oxidative stress.
- TRPML1 downregulation led to mitochondrial damage in MCs exposed to oxidative stress.
Conclusions:
- TRPML1 mediates lysosomal autophagy in primary human MCs during oxidative stress.
- TRPML1 contributes to maintaining the balance of oxidative and antioxidant systems in melanocytes.
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