{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T23:32:49Z","timestamp":1785713569359,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6-2016-0139"],"award-info":[{"award-number":["6-2016-0139"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxic conditions induce the activation of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) to restore the supply of oxygen to tissues and cells. Activated HIF-1\u03b1 translocates into the nucleus and binds to hypoxia response elements to promote the transcription of target genes. Cathepsin L (CTSL) is a lysosomal protease that degrades cellular proteins via the endolysosomal pathway. In this study, we attempted to determine if CTSL is a hypoxia responsive target gene of HIF-1\u03b1, and decipher its role in melanocytes in association with the autophagic pathway. The results of our luciferase reporter assay showed that the expression of CTSL is transcriptionally activated through the binding of HIF1-\u03b1 at its promoter. Under autophagy-inducing starvation conditions, HIF-1\u03b1 and CTSL expression is highly upregulated in melan-a cells. The mature form of CTSL is closely involved in melanosome degradation through lysosomal activity upon autophagosome\u2013lysosome fusion. The inhibition of conversion of pro-CTSL to mature CTSL leads to the accumulation of gp100 and tyrosinase in addition to microtubule-associated protein 1 light chain 3 (LC3) II, due to decreased lysosomal activity in the autophagic pathway. In conclusion, we have identified that CTSL, a novel target of HIF-1\u03b1, participates in melanosome degradation in melanocytes through lysosomal activity during autophagosome\u2013lysosome fusion.<\/jats:p>","DOI":"10.3390\/ijms22168596","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T08:57:14Z","timestamp":1628585834000},"page":"8596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cathepsin L, a Target of Hypoxia-Inducible Factor-1-\u03b1, Is Involved in Melanosome Degradation in Melanocytes"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6217-321X","authenticated-orcid":false,"given":"Ji Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-2652","authenticated-orcid":false,"given":"Eun Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Graduate School of Medical Science, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7675-4402","authenticated-orcid":false,"given":"Sujin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-600X","authenticated-orcid":false,"given":"Yu Jeong","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2116-4579","authenticated-orcid":false,"given":"Tae Gyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ho","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Graduate School of Medical Science, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cell.2012.01.021","article-title":"Hypoxia-Inducible Factors in Physiology and Medicine","volume":"148","author":"Semenza","year":"2012","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"112274","DOI":"10.1016\/j.ejmech.2020.112274","article-title":"Hypoxia-activated nanomedicines for effective cancer therapy","volume":"195","author":"Zhou","year":"2020","journal-title":"Eur. 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