Peroxisome Membrane Protein PEX16 Inhibits Melanogenesis by Inhibiting the Wnt/β-Catenin Signalling Pathway

Xiaolei Duan1, Yibo Hu2, Chuhan Fu1

  • 1Department of Dermatology, Third Xiangya Hospital of Central South University, Changsha, China.

Experimental Dermatology
|January 10, 2026
PubMed

Insights

Peroxisomal biogenesis factor 16 (PEX16) inhibits melanin production by reducing melanogenesis. Higher PEX16 expression correlates with lower pigmentation, offering new therapeutic targets for skin disorders.

Area of Science:

  • Dermatology
  • Cell Biology
  • Molecular Biology

Background:

  • Melanogenesis, the process of melanin production, is crucial for skin pigmentation and is implicated in various skin disorders.
  • Peroxisomes are vital organelles involved in cellular metabolism, but their role in melanogenesis is not fully understood.

Purpose of the Study:

  • To investigate the relationship between peroxisomes, specifically peroxisomal biogenesis factor 16 (PEX16), and melanin synthesis.
  • To elucidate the molecular mechanisms by which PEX16 influences melanogenesis and its potential as a therapeutic target for pigmentation disorders.

Main Methods:

  • Analysis of omics data and clinical skin samples.
  • Overexpression of PEX16 in MNT1 cell lines and primary melanocytes.
  • Quantitative analysis of melanin content and gene expression (MITF, TYR, TYRP1, DCT).
  • Detection of PEX16 expression in human skin tissues and assessment after UVB irradiation.
  • Investigation of the Wnt/β-catenin signaling pathway.

Main Results:

  • PEX16 expression was negatively associated with melanogenesis.
  • Overexpression of PEX16 increased peroxisome production and inhibited key melanogenesis genes (MITF, TYR, TYRP1, DCT).
  • PEX16 overexpression in melanocytes significantly reduced melanin content.
  • PEX16 expression was higher in less pigmented skin areas and decreased after UVB exposure.
  • PEX16 was found to suppress the Wnt/β-catenin signaling pathway.

Conclusions:

  • PEX16 inhibits melanogenesis by suppressing the Wnt/β-catenin signaling pathway.
  • PEX16 plays a significant role in regulating skin pigmentation.
  • PEX16 represents a potential therapeutic target for managing skin pigmentation disorders.

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.4K
Protein Import into the Peroxisomes01:27

Protein Import into the Peroxisomes

Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
5.2K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
3.0K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K
Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
19.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.2K