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European Journal of Dermatology : EJD Dec 2020Hyperpigmentation and hypopigmentation are two manifestations of skin pigmentation diseases. Recent studies have shown that autophagy is involved in the development of... (Review)
Review
Hyperpigmentation and hypopigmentation are two manifestations of skin pigmentation diseases. Recent studies have shown that autophagy is involved in the development of skin pigmentation diseases. The melanosome is a lysosome-related organelle characterized by the production of melanin. The autophagosome-lysosome degradation pathway exhibits a characteristic cell renewal function. The functions of melanosomes and autophagosomes intersect and the vesicle transport pathway mediates both autophagosome and melanosome formation, which may involve different regulatory protein complexes. Current studies have revealed that several autophagy-related regulators of autophagosome formation are involved in melanosome formation and maturation and also regulate melanogenesis, and that melanosomes can be degraded via autophagy in melanocytes. Autophagy is also involved in regulating the living environment of melanocytes. Understanding the effects of autophagy on pigmentation may support our understanding of pigmentation diseases. This article reviews the relationship between autophagy and pigmentation in melanocytes.
Topics: Autophagy; Humans; Melanocytes; Melanosomes; Pigmentation Disorders; Skin Pigmentation
PubMed: 33262098
DOI: 10.1684/ejd.2020.3930 -
Frontiers in Oncology 2022
PubMed: 36505857
DOI: 10.3389/fonc.2022.1084717 -
Acta Dermato-venereologica Jun 2020Cutaneous melanoma arises from melanocytes following genetic, epigenetic and allogenetic (i.e. other than epi/genetic) modifications. An estimated 10% of cutaneous... (Review)
Review
Cutaneous melanoma arises from melanocytes following genetic, epigenetic and allogenetic (i.e. other than epi/genetic) modifications. An estimated 10% of cutaneous melanoma cases are due to inherited variants or de novo mutations in approximately 20 genes, found using linkage, next-generation sequencing and association studies. Based on these studies, 3 classes of predisposing melanoma genes have been defined based on the frequency of the variants in the general population and lifetime risk of developing a melanoma: (i) ultra-rare variants with a high risk, (ii) rare with a moderate risk, and (iii) frequent variants with a low risk. Most of the proteins encoded by these genes have been shown to be involved in melanoma initiation, including proliferation and senescence bypass. This paper reviews the role(s) of these genes in the transformation of melanocytes into melanoma. It also describes their function in the establishment and renewal of melanocytes and the biology of pigment cells, if known.
Topics: Animals; Biomarkers, Tumor; Cell Lineage; Genetic Predisposition to Disease; Humans; Melanins; Melanocytes; Melanoma; Melanosomes; Mutation; Mutation Rate; Phenotype; Risk Assessment; Risk Factors; Skin Neoplasms; White People
PubMed: 32346747
DOI: 10.2340/00015555-3494 -
Biochemical Society Transactions Aug 2018Historically, studies on the maturation and intracellular transport of melanosomes in melanocytes have greatly contributed to elucidating the general mechanisms of... (Review)
Review
Historically, studies on the maturation and intracellular transport of melanosomes in melanocytes have greatly contributed to elucidating the general mechanisms of intracellular transport in many different types of mammalian cells. During melanosome maturation, melanosome cargoes including melanogenic enzymes (e.g. tyrosinase) are transported from endosomes to immature melanosomes by membrane trafficking, which must require a membrane fusion process likely regulated by SNAREs [oluble SF (-ethylmaleimide-sensitive factor) ttachment protein ceptors]. In the present study, we review the literature concerning the expression and function of SNAREs (e.g. v-SNARE vesicle-associated membrane protein 7 and t-SNAREs syntaxin-3/13 and synaptosomal-associated protein-23) in melanocytes, especially in regard to the fusion process in which melanosome cargoes are finally delivered to immature melanosomes. We also describe the recent discovery of the SNARE recycling system on mature melanosomes in melanocytes. Such SNARE dynamics, especially the SNARE recycling system, on melanosomes will be useful in understanding as yet unidentified SNARE dynamics on other organelles.
Topics: Animals; Carrier Proteins; Humans; Melanosomes; Membrane Fusion; Organelles; Protein Transport; SNARE Proteins
PubMed: 30026369
DOI: 10.1042/BST20180130 -
Trends in Ecology & Evolution May 2021Melanins are widespread pigments in vertebrates, with important roles in visual signaling, UV protection, and homeostasis. Fossil evidence of melanin and melanin-bearing... (Review)
Review
Melanins are widespread pigments in vertebrates, with important roles in visual signaling, UV protection, and homeostasis. Fossil evidence of melanin and melanin-bearing organelles - melanosomes - in ancient vertebrates may illuminate the evolution of melanin and its functions, but macroevolutionary trends are poorly resolved. Here, we integrate fossil data with current understanding of melanin function, biochemistry, and genetics. Mapping key genes onto phenotypic attributes of fossil vertebrates identifies potential genomic controls on melanin evolution. Taxonomic trends in the anatomical location, geometry, and chemistry of vertebrate melanosomes are linked to the evolution of endothermy. These shifts in melanin biology suggest fundamental links between melanization and vertebrate ecology. Tissue-specific and taxonomic trends in melanin chemistry support evidence for evolutionary tradeoffs between function and cytotoxicity.
Topics: Animals; Fossils; Melanins; Melanosomes; Pigmentation; Vertebrates
PubMed: 33549373
DOI: 10.1016/j.tree.2020.12.012 -
Autophagy Feb 2019Ultraviolet radiation (UVR)-induced skin pigmentation, afforded by the dark organelles termed melanosomes, accounts for the first-line protection against environmental...
Ultraviolet radiation (UVR)-induced skin pigmentation, afforded by the dark organelles termed melanosomes, accounts for the first-line protection against environmental UVR that increases the risk of developing skin cancers including melanoma. We have recently discovered that UVRAG, originally identified as a BECN1-binding macroautophagy/autophagy protein, appears to have a specialized function in melanosome biogenesis beyond autophagy through its interaction with the biogenesis of lysosome-related organelles complex 1 (BLOC-1). This melanogenic function of UVRAG is controlled by the melanocyte-specific transcription factor MITF as a downstream effector of the α-melanocyte-stimulating hormone (α-MSH)-cAMP signaling in the suntan response, which is compromised in BRAF mutant melanoma. Thus we propose a new mode of UVRAG activity and regulation in melanocyte biology that may affect melanoma predisposition.
Topics: Beclin-1; Humans; Melanins; Melanocytes; Melanosomes; Skin Pigmentation; Tumor Suppressor Proteins; Ultraviolet Rays
PubMed: 30209981
DOI: 10.1080/15548627.2018.1522911 -
Cells Jun 2022Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of... (Review)
Review
Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of melanin and are transferred from melanocytes to keratinocytes. The relatively well-known process by which melanin is synthesized from melanocytes is known as melanogenesis. The relationship between melanogenesis and autophagy is attracting the attention of researchers because proteins associated with autophagy, such as WD repeat domain phosphoinositide-interacting protein 1, microtubule-associated protein 1 light chain 3, autophagy-related (ATG)7, ATG4, beclin-1, and UV-radiation resistance-associated gene, contribute to the melanogenesis signaling pathway. Additionally, there are reports that some compounds used as whitening cosmetics materials induce skin depigmentation through autophagy. Thus, the possibility that autophagy is involved in the removal of melanin has been suggested. To date, however, there is a lack of data on melanosome autophagy and its underlying mechanism. This review highlights the importance of autophagy in melanin homeostasis by providing an overview of melanogenesis, autophagy, the autophagy machinery involved in melanogenesis, and natural compounds that induce autophagy-mediated depigmentation.
Topics: Autophagy; Homeostasis; Melanins; Melanocytes; Melanosomes
PubMed: 35805169
DOI: 10.3390/cells11132085 -
Seminars in Cell & Developmental Biology Apr 2016In this review, I will discuss how careful scrutiny of genetic skin disorders could help us to understand human biology. Like other organs, the skin and its appendages,... (Review)
Review
In this review, I will discuss how careful scrutiny of genetic skin disorders could help us to understand human biology. Like other organs, the skin and its appendages, such as hairs and teeth, experience fundamental biological processes ranging from lipid metabolism to vesicular transport and cellular migration. However, in contrast to other organ systems, they are accessible and can be studied with relative ease. By visually revealing the functional consequences of single gene defects, genetic skin diseases offer a unique opportunity to study human biology. Here, I will illustrate this concept by discussing how human genetic disorders of skin pigmentation reflect the mechanisms underlying this complex and vital process.
Topics: Animals; Humans; Melanosomes; Skin Diseases; Skin Pigmentation
PubMed: 26877141
DOI: 10.1016/j.semcdb.2016.02.013 -
Cells Nov 2022Lysosome-related organelles (LROs) are a group of functionally diverse, cell type-specific compartments. LROs include melanosomes, alpha and dense granules, lytic... (Review)
Review
Lysosome-related organelles (LROs) are a group of functionally diverse, cell type-specific compartments. LROs include melanosomes, alpha and dense granules, lytic granules, lamellar bodies and other compartments with distinct morphologies and functions allowing specialised and unique functions of their host cells. The formation, maturation and secretion of specific LROs are compromised in a number of hereditary rare multisystem disorders, including Hermansky-Pudlak syndromes, Griscelli syndrome and the Arthrogryposis, Renal dysfunction and Cholestasis syndrome. Each of these disorders impacts the function of several LROs, resulting in a variety of clinical features affecting systems such as immunity, neurophysiology and pigmentation. This has demonstrated the close relationship between LROs and led to the identification of conserved components required for LRO biogenesis and function. Here, we discuss aspects of this conserved machinery among LROs in relation to the heritable multisystem disorders they associate with, and present our current understanding of how dysfunctions in the proteins affected in the disease impact the formation, motility and ultimate secretion of LROs. Moreover, we have analysed the expression of the members of the CHEVI complex affected in Arthrogryposis, Renal dysfunction and Cholestasis syndrome, in different cell types, by collecting single cell RNA expression data from the human protein atlas. We propose a hypothesis describing how transcriptional regulation could constitute a mechanism that regulates the pleiotropic functions of proteins and their interacting partners in different LROs.
Topics: Humans; Arthrogryposis; Lysosomes; Melanosomes; Rare Diseases; Cholestasis; Kidney Diseases
PubMed: 36429129
DOI: 10.3390/cells11223702 -
PLoS Genetics Mar 2018PIKfyve, VAC14, and FIG4 form a complex that catalyzes the production of PI(3,5)P2, a signaling lipid implicated in process ranging from lysosome maturation to...
PIKfyve, VAC14, and FIG4 form a complex that catalyzes the production of PI(3,5)P2, a signaling lipid implicated in process ranging from lysosome maturation to neurodegeneration. While previous studies have identified VAC14 and FIG4 mutations that lead to both neurodegeneration and coat color defects, how PIKfyve regulates melanogenesis is unknown. In this study, we sought to better understand the role of PIKfyve in melanosome biogenesis. Melanocyte-specific PIKfyve knockout mice exhibit greying of the mouse coat and the accumulation of single membrane vesicle structures in melanocytes resembling multivesicular endosomes. PIKfyve inhibition blocks melanosome maturation, the processing of the melanosome protein PMEL, and the trafficking of the melanosome protein TYRP1. Taken together, these studies identify a novel role for PIKfyve in controlling the delivery of proteins from the endosomal compartment to the melanosome, a role that is distinct from the role of PIKfyve in the reformation of lysosomes from endolysosomes.
Topics: Animals; Flavoproteins; Intracellular Signaling Peptides and Proteins; Melanins; Melanosomes; Membrane Proteins; Mice; Mice, Knockout; Organelles; Phosphatidylinositol 3-Kinases; Phosphoinositide Phosphatases; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Protein Transport
PubMed: 29584722
DOI: 10.1371/journal.pgen.1007290