The metabolism of melanin synthesis—From melanocytes to melanoma

Pigment Cell & Melanoma Research, Год журнала: 2024, Номер 37(4), С. 438 - 452

Опубликована: Март 6, 2024

Melanin synthesis involves the successful coordination of metabolic pathways across multiple intracellular compartments including melanosome, mitochondria, ER/Golgi, and cytoplasm. While pigment production offers a communal protection from UV damage, process also requires anabolic redox demands that must be carefully managed by melanocytes. In this report we provide an updated review on melanin metabolism, recent data leveraging new techniques, technologies in field metabolism. We discuss many aspects intersect with known to impact melanoma phenotypes behavior. By reviewing metabolism synthesis, hope highlight outstanding questions opportunities for future research could improve patient outcomes pigmentary oncologic disease settings.

Язык: Английский

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Melanosome Biogenesis in the Pigmentation of Mammalian Skin

Integrative and Comparative Biology, Год журнала: 2021, Номер 61(4), С. 1517 - 1545

Опубликована: Май 21, 2021

Melanins, the main pigments of skin and hair in mammals, are synthesized within membrane-bound organelles melanocytes called melanosomes. Melanosome structure function determined by a cohort resident transmembrane proteins, many which expressed only pigment cells localize specifically to Defects genes that encode melanosome-specific proteins or components machinery required for their transport out melanosomes underlie various forms ocular oculocutaneous albinism, characterized hypopigmentation hair, skin, eyes visual impairment. We review major melanosomes, including enzymes catalyze steps melanin synthesis from tyrosine precursors, solute transporters allow these function, structural melanosome shape deposition. then molecular mechanisms biosynthetically delivered newly forming melanosomes-many shared other cell types generate type-specific lysosome-related organelles. also highlight unanswered questions need be addressed future investigation.

Язык: Английский

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Determinants, maintenance, and function of organellar pH

Physiological Reviews, Год журнала: 2022, Номер 103(1), С. 515 - 606

Опубликована: Авг. 18, 2022

The protonation state of soluble and membrane-associated macromolecules dictates their charge, conformation, functional activity. In addition, protons (H + or equivalents) partake in numerous metabolic reactions serve as a source electrochemical energy to drive the transmembrane transport both organic inorganic substrates. Stringent regulation intracellular pH is therefore paramount homeostasis. Although cytosolic has been studied extensively, our understanding determinants H concentration ([H ]) organelles developed more slowly, limited by small size inaccessibility. Recently, however, targeting molecular probes organellar lumen together with advances genomic, proteomic, electrophysiological techniques have led identification characterization unique pumps, channels, transporters responsible for establishment maintenance intraorganellar pH. These developments implications cellular function health disease are subject this review.

Язык: Английский

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The retinal pigmentation pathway in human albinism: Not so black and white

Progress in Retinal and Eye Research, Год журнала: 2022, Номер 91, С. 101091 - 101091

Опубликована: Июнь 18, 2022

Albinism is a pigment disorder affecting eye, skin and/or hair. Patients usually have decreased melanin in affected tissues and suffer from severe visual abnormalities, including foveal hypoplasia chiasmal misrouting. Combining our data with those of the literature, we propose single functional genetic retinal signalling pathway that includes all 22 currently known human albinism disease genes. We hypothesise defects genesis or function different intra-cellular organelles, melanosomes, cause syndromic forms (Hermansky-Pudlak (HPS) Chediak-Higashi syndrome (CHS)). put forward specific melanosome impairments oculocutaneous (OCA1-8). Further, incorporate GPR143 has been implicated ocular (OA1), characterised by phenotype limited to eye. Finally, include SLC38A8-associated FHONDA causes an even more restricted "albinism-related" misrouting but without pigmentation defects. following pathway, increasingly cellular causing phenotype: (HPS1-11/CHS: albinism)-(OCA1-8: OCA)-(GPR143: OA1)-(SLC38A8: FHONDA). Beyond genes involvement, also evaluate range (candidate) regulatory mechanisms activity development, albinism. further suggest proposed involved other disorders, such as age-related macular degeneration. The hypotheses this report provide framework for systematic studies disorders.

Язык: Английский

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Chemical and biochemical control of skin pigmentation with special emphasis on mixed melanogenesis

Pigment Cell & Melanoma Research, Год журнала: 2021, Номер 34(4), С. 730 - 747

Опубликована: Март 10, 2021

Melanins are widely distributed in animals and plants; vertebrates, most melanins present on the body surface. The diversity of pigmentation vertebrates is mainly attributed to quantity ratio eumelanin pheomelanin synthesis. Most natural melanin pigments consist both varying ratios, thus, their combined synthesis called "mixed melanogenesis." Gene expression an established mechanism for controlling synthesis; however, there multiple factors that affect besides gene expression. Due differential sensitivity synthetic pathways pH, melanosomal pH likely plays a major role mixed melanogenesis. Here, we focused various affecting melanogenesis including (1) chemical regulation synthesis, (2) during normal effect melanogenesis, (3) mechanisms control (proton pumps, channels, transporters, signaling pathways).

Язык: Английский

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Genetics of non‐syndromic and syndromic oculocutaneous albinism in human and mouse

Pigment Cell & Melanoma Research, Год журнала: 2021, Номер 34(4), С. 786 - 799

Опубликована: Май 8, 2021

Abstract Oculocutaneous albinism (OCA) is the most frequent presentation of albinism, a heterogeneous rare genetic condition generally associated with variable alterations in pigmentation and profound visual impairment. There are non‐syndromic syndromic types OCA, depending on whether gene product affected impairs essentially function melanosomes or, addition, that other lysosome‐related organelles (LROs), respectively. Syndromic OCA can be more severe additional systemic consequences, beyond vision alterations. In addition to also presented without obvious skin hair alterations, ocular (OA), related known as foveal hypoplasia, optic nerve decussation defects, anterior segment dysgenesis (FHONDA). this review, we will focus only genetics both human mouse, updating our current knowledge subject.

Язык: Английский

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Genome-wide association study on milk production and somatic cell score for Thai dairy cattle using weighted single-step approach with random regression test-day model

Journal of Dairy Science, Год журнала: 2021, Номер 105(1), С. 468 - 494

Опубликована: Окт. 28, 2021

Genome-wide association studies are a powerful tool to identify genomic regions and variants associated with phenotypes. However, only limited mutual confirmation from different is available. The objectives of this study were as well genes pathways the first-lactation milk, fat, protein, total solid yields; percentage; somatic cell score (SCS) in Thai dairy cattle population. Effects SNPs estimated by weighted single-step GWAS, which back-solved breeding values predicted using BLUP (ssGBLUP) fitting single-trait random regression test-day model. Genomic that explained at least 0.5% genetic variance selected for further analyses candidate genes. Despite small number genotyped animals, predictions led an improvement accuracy over traditional BLUP. ssGBLUP slightly better than ssGBLUP. milk production traits contained 210 on 19 chromosomes [Bos taurus autosome (BTA) 1 7, 9, 11 16, 20 21, 26 27 29], whereas 21 3 (BTA 11, 21) SCS. Many fraction variance, indicating polygenic inheritance studied traits. Several coincided previous reports Holstein cattle, especially large region BTA14. We identified 141 5 novel related SCS, respectively. These also found be functionally heat tolerance (e.g., SLC45A2, IRAG1, LOC101902172), longevity SYT10 LOC101903327), fertility PAG1). findings may attributed indirect selection our Identified biological networks including intracellular transportation protein catabolism implicate production, immunological such lymphocyte activation closely Further required validate before exploiting them selection.

Язык: Английский

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Analysis of the genetic loci of pigment pattern evolution in vertebrates

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Год журнала: 2023, Номер 98(4), С. 1250 - 1277

Опубликована: Апрель 5, 2023

ABSTRACT Vertebrate pigmentation patterns are amongst the best characterised model systems for studying genetic basis of adaptive evolution. The wealth available data on evolution allows analysis trends and quantitative testing evolutionary hypotheses. We employed Gephebase , a database variants associated with natural domesticated trait variation, to examine in how cis ‐regulatory coding mutations contribute vertebrate phenotypes, as well factors that favour one mutation type over other. found studies lower ascertainment bias identified higher proportions mutations, were more common animals harbouring number pigment cell classes. classified traits firstly according their physiological secondly whether they affect colour or pattern, carotenoid‐based variation pattern boundaries preferentially change. also genes developmental, cellular, molecular functions. greater proportion implicated upstream developmental processes compared those involved downstream cellular functions, ligands than respective receptors. Based these trends, we discuss future directions research

Язык: Английский

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Skin colour: A window into human phenotypic evolution and environmental adaptation

Molecular Ecology, Год журнала: 2024, Номер 33(12)

Опубликована: Май 7, 2024

As modern humans ventured out of Africa and dispersed around the world, they faced novel environmental challenges that led to geographic adaptations including skin colour. Over long history human evolution, colour has changed dramatically, showing tremendous diversity across different geographical regions, for example, majority individuals from expansive lands have darker skin, whereas people Eurasia exhibit lighter skin. What did confer upon as migrated Eurasia? genetic mechanisms underlie observed in populations? In recent years, scientists gradually gained a deeper understanding interactions between pigmentation gene through population-based genomic studies groups particularly East Asia Africa. this review, we summarize our current 26 colour-related genes 48 SNPs influence Important three major populations are described detail: MFSD12, SLC24A5, PDPK1 DDB1/CYB561A3/TMEM138 African populations; OCA2, KITLG, SLC24A2, GNPAT PAH key evolution Asian SLC45A2, TYR, TYRP1, ASIP, MC1R IRF4 significantly contribute lightening European populations. We summarized findings implicate diverse environments, local adaptation among populations, flow multi-gene factors influencing diversity.

Язык: Английский

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Mapping chromatin interactions at melanoma susceptibility loci uncovers distant cis-regulatory gene targets

The American Journal of Human Genetics, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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