{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:06:06Z","timestamp":1761653166972,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sichuan Freshwater Fish Innovation Team Construction Project of China Agriculture Research System","award":["SCCXTD-2025-15"],"award-info":[{"award-number":["SCCXTD-2025-15"]}]},{"name":"Technology Program of Sichuan Academy of Agricultural Sciences","award":["1+9KJGG004"],"award-info":[{"award-number":["1+9KJGG004"]}]},{"name":"Project of Sichuan Science and Technology Program","award":["2021YFYZ0015"],"award-info":[{"award-number":["2021YFYZ0015"]}]},{"name":"Agricultural frontier technology research project of Sichuan Academy of Agricultural Sciences","award":["5+1QYGG006"],"award-info":[{"award-number":["5+1QYGG006"]}]},{"name":"Natural Science Foundation project","award":["2025ZNSFSC1078"],"award-info":[{"award-number":["2025ZNSFSC1078"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Percocypris pingi is an endangered protected fish species in China. Its albino variants exhibit growth retardation and physiological abnormalities. Understanding its albinism mechanism holds significant scientific importance for molecular breeding programs and disease model development. This study integrated transcriptomic and proteomic analyses, combined with histopathological and molecular biological techniques, to systematically compare molecular differences in skin tissues between albino and wild-type P. pingi, with a focus on elucidating the multidimensional regulatory mechanisms underlying skin albinism. Our findings suggest that albinism in P. pingi is synergistically driven by hyperactivation of ubiquitin-mediated proteolysis (which suppressed TYR\/TYRP1 enzymatic activity and disrupted the pH homeostasis of melanosomes), and inhibition of calcium signaling (which impeded melanin transport). This discovery provides novel insights into the mechanisms of pigment loss in fish species and offers a valuable reference for molecular breeding of endangered species as well as research on pigmentation-related disorders.<\/jats:p>","DOI":"10.3390\/cells14211684","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T11:47:19Z","timestamp":1761652039000},"page":"1684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Omics Analysis of the Potential Mechanisms of Skin Albinism in Edangered Percocypris pingi: Abnormal Ubiquitination and Calcium Signal Inhibition"],"prefix":"10.3390","volume":"14","author":[{"given":"Senyue","family":"Liu","sequence":"first","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"},{"name":"Aquatic Health and Intelligent Aquaculture Key Laboratory of Sichuan Province, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaolin","family":"Zou","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiansheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyun","family":"Ni","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1067-8193","authenticated-orcid":false,"given":"Yongqiang","family":"Deng","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"},{"name":"Aquatic Health and Intelligent Aquaculture Key Laboratory of Sichuan Province, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Feng","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"},{"name":"Aquatic Health and Intelligent Aquaculture Key Laboratory of Sichuan Province, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjiang","family":"Song","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengcheng","family":"Li","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Du","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"},{"name":"Aquatic Health and Intelligent Aquaculture Key Laboratory of Sichuan Province, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2744-9049","authenticated-orcid":false,"given":"Ya","family":"Liu","sequence":"additional","affiliation":[{"name":"Fisheries Research Institute, Sichuan Academy of Agricultural Sciences (Sichuan Fisheries Research Institute), Chengdu 611731, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/S1357-2725(97)00013-7","article-title":"Melanin","volume":"29","author":"Riley","year":"1997","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/jid.2013.487","article-title":"Melanin transfer: The keratinocytes are more than gluttons","volume":"134","author":"Delevoye","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/pcmr.12970","article-title":"Chemical and biochemical control of skin pigmentation with special emphasis on mixed melanogenesis","volume":"34","author":"Wakamatsu","year":"2021","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.3390\/ijms10062440","article-title":"An updated review of tyrosinase inhibitors","volume":"10","author":"Chang","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guo, L., Li, W., Gu, Z., Wang, L., Guo, L., Ma, S., Li, C., Sun, J., Han, B., and Chang, J. (2023). Recent advances and progress on melanin: From source to application. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054360"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1468-3083.2003.00767.x","article-title":"Oculocutaneous albinism","volume":"17","author":"Okulicz","year":"2003","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chang, L., Zhu, W., and Jiang, J. (2022). Albinism in the largest extant amphibian: A metabolic, endocrine, or immune problem?. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1053732"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.3390\/ijms10104428","article-title":"Role of the ubiquitin proteasome system in regulating skin pigmentation","volume":"10","author":"Ando","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11906","DOI":"10.1073\/pnas.1103381108","article-title":"The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function","volume":"108","author":"Giordano","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/path.6201","article-title":"Conditional loss of Ube3d in the retinal pigment epithelium accelerates age-associated alterations in the retina of mice","volume":"261","author":"Tao","year":"2023","journal-title":"J. Pathol."},{"key":"ref_11","first-page":"112","article-title":"Melanin\u2019s journey from melanocytes to keratinocytes: Uncovering the molecular mechanisms of melanin transfer and processing","volume":"24","author":"Charneca","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/pcmr.12931","article-title":"Rab GTPases: Key players in melanosome biogenesis, transport, and transfer","volume":"34","author":"Fukuda","year":"2021","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107707","DOI":"10.1016\/j.pharmthera.2020.107707","article-title":"Melanosome transport and regulation in development and disease","volume":"219","author":"Tian","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_14","first-page":"40","article-title":"Red list of China\u2019s vertebrates","volume":"24","author":"Jiang","year":"2016","journal-title":"Biol. Div."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1186\/s12864-024-11100-9","article-title":"The whole chromosome-level genome provides resources and insights into the endangered fish Percocypris pingi evolution and conservation","volume":"25","author":"He","year":"2024","journal-title":"BMC Genom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-1050-2_3","article-title":"Tissue processing and hematoxylin and eosin staining","volume":"1180","author":"Feldman","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12964-025-02116-z","article-title":"Increased melanin induces aberrant keratinocyte-melanocyte-basal-fibroblast cell communication and fibrogenesis by inducing iron overload and ferroptosis resistance in keloids","volume":"23","author":"Shi","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nbt.1883","article-title":"Full-length transcriptome assembly from RNA-Seq data without a reference genome","volume":"29","author":"Grabherr","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinform."},{"key":"ref_20","first-page":"11","article-title":"The Benjamini-Hochberg method in the case of discrete test statistics","volume":"3","author":"Ferreira","year":"2007","journal-title":"Int. J. Biostat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.fsi.2021.11.021","article-title":"Characterization of reference genes for qRT-PCR normalization in rice-field eel (Monopterus albus) to assess differences in embryonic developmental stages, the early development of immune organs, and cells infected with rhabdovirus","volume":"120","author":"Liu","year":"2022","journal-title":"Fish Shellfish Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/jfb.13986","article-title":"Evaluation of reference genes for quantitative real-time PCR analysis of messenger RNAs and microRNAs in rainbow trout Oncorhynchus mykiss under heat stress","volume":"95","author":"Ma","year":"2019","journal-title":"J. Fish Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/14756366.2016.1256882","article-title":"Skin whitening agents: Medicinal chemistry perspective of tyrosinase inhibitors","volume":"32","author":"Pillaiyar","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejmech.2018.10.025","article-title":"Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in \u03b1-MSH-stimulated B16F10 melanoma cells","volume":"161","author":"Ullah","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3390\/cosmetics4040043","article-title":"Degradation of Tyrosinase by Melanosomal pH Change and a New Mechanism of Whitening with Propylparaben","volume":"4","author":"Zeng","year":"2017","journal-title":"Cosmetics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1006\/excr.2001.5251","article-title":"Melanosomal pH controls rate of melanogenesis, eumelanin\/phaeomelanin ratio and melanosome maturation in melanocytes and melanoma cells","volume":"268","author":"Ancans","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1006\/excr.2000.5092","article-title":"Regulation of the catalytic activity of preexisting tyrosinase in black and Caucasian human melanocyte cell cultures","volume":"262","author":"Fuller","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.yexcr.2004.04.033","article-title":"The relationship between Na(+)\/H(+) exchanger expression and tyrosinase activity in human melanocytes","volume":"298","author":"Smith","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/pcmr.12053","article-title":"Slc45a2 and V-ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease","volume":"26","author":"Dooley","year":"2013","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bin, B.H., Bhin, J., Yang, S.H., Shin, M., Nam, Y.J., Choi, D.H., Shin, D.W., Lee, A.Y., Hwang, D., and Cho, E.G. (2015). Membrane-associated transporter protein (matp) regulates melanosomal ph and influences tyrosinase activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129273"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41418-020-00703-w","article-title":"The ubiquitin system: From cell signalling to disease biology and new therapeutic opportunities","volume":"28","author":"Damgaard","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1755-148X.2010.00692.x","article-title":"Growth and progression of melanoma and non-melanoma skin cancers regulated by ubiquitination","volume":"23","author":"Nakayama","year":"2010","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/j.1755-148X.2011.00884.x","article-title":"UBE3A regulates MC1R expression: A link to hypopigmentation in Angelman syndrome","volume":"24","author":"Low","year":"2011","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1600-0749.2007.00376.x","article-title":"Myosins in melanocytes: To move or not to move?","volume":"20","author":"Coudrier","year":"2007","journal-title":"Pigment Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Castellano-Pellicena, I., Morrison, C.G., Bell, M., O\u2019Connor, C., and Tobin, D.J. (2021). Melanin distribution in human skin: Influence of cytoskeletal, polarity, and centrosome-related machinery of stratum basale keratinocytes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063143"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18937","DOI":"10.1073\/pnas.1911452116","article-title":"Assemblies of calcium\/calmodulin-dependent kinase II with actin and their dynamic regulation by calmodulin in dendritic spines","volume":"116","author":"Wang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1038\/s41467-022-30167-0","article-title":"Calcium bursts allow rapid reorganization of EFhD2\/Swip-1 cross-linked actin networks in epithelial wound closure","volume":"13","author":"Lehne","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1083\/jcb.200111012","article-title":"The endoplasmic reticulum cation P-type ATPase Cta4p is required for control of cell shape and microtubule dynamics","volume":"157","author":"Appelgren","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1091\/mbc.e06-02-0112","article-title":"Sonderegger. Calsyntenin-1 docks vesicular cargo to kinesin-1","volume":"17","author":"Konecna","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1600-0749.1993.tb00620.x","article-title":"Calcium plays a complex role in the regulation of melanogenesis in murine B16 melanoma cells","volume":"6","author":"Buffey","year":"1993","journal-title":"Pigment Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.2007.00226.x","article-title":"The protective role of melanin against UV damage in human skin","volume":"84","author":"Brenner","year":"2008","journal-title":"Photochem. Photobiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/21\/1684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:01:21Z","timestamp":1761652881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/21\/1684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":42,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cells14211684"],"URL":"https:\/\/doi.org\/10.3390\/cells14211684","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,27]]}}}