{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:04:48Z","timestamp":1778177088411,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB850"],"award-info":[{"award-number":["SFB850"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHI 871\/11-1; PA 2807\/3-1; SCHI 871\/9-1; SCHI 871\/8-1;GR 1748\/6-1;"],"award-info":[{"award-number":["SCHI 871\/11-1; PA 2807\/3-1; SCHI 871\/9-1; SCHI 871\/8-1;GR 1748\/6-1;"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>DJ-1 is an abundant and ubiquitous component of cellular proteomes. DJ-1 supposedly exerts a wide variety of molecular functions, ranging from enzymatic activities as a deglycase, protease, and esterase to chaperone functions. However, a consensus perspective on its molecular function in the cellular context has not yet been reached. Structurally, the C-terminal helix 8 of DJ-1 has been proposed to constitute a propeptide whose proteolytic removal transforms a DJ-1 zymogen to an active hydrolase with potential proteolytic activity. To better understand the cell-contextual functionality of DJ-1 and the role of helix 8, we employed post-mitotically differentiated, neuron-like SH-SY5Y neuroblastoma cells with stable over-expression of full length DJ-1 or DJ-1 lacking helix 8 (\u0394H8), either with a native catalytically active site (C106) or an inactive site (C106A active site mutation). Global proteome comparison of cells over-expressing DJ-1 \u0394H8 with native or mutated active site cysteine indicated a strong impact on mitochondrial biology. N-terminomic profiling however did not highlight direct protease substrate candidates for DJ-1 \u0394H8, but linked DJ-1 to elevated levels of activated lysosomal proteases, albeit presumably in an indirect manner. Finally, we show that DJ-1 \u0394H8 loses the deglycation activity of full length DJ-1. Our study further establishes DJ-1 as deglycation enzyme. Helix 8 is essential for the deglycation activity but dispensable for the impact on lysosomal and mitochondrial biology; further illustrating the pleiotropic nature of DJ-1.<\/jats:p>","DOI":"10.3390\/cells10020404","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T08:09:09Z","timestamp":1613462949000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of DJ-1 and Helix 8 on the Proteome and Degradome of Neuron-Like Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Ursula","family":"Kern","sequence":"first","affiliation":[{"name":"Institute of Surgical Pathology, Medical Center, University of Freiburg, Breisacher Stra\u00dfe 115a, D-79106 Freiburg, Germany"},{"name":"Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klemens","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[{"name":"Institute of Surgical Pathology, Medical Center, University of Freiburg, Breisacher Stra\u00dfe 115a, D-79106 Freiburg, Germany"},{"name":"Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Bedacht","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Biniossek","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Gensch","sequence":"additional","affiliation":[{"name":"Core Facility Signalling Factory, BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-9440","authenticated-orcid":false,"given":"Katja","family":"Baerenfaller","sequence":"additional","affiliation":[{"name":"Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and Swiss Institute of Bioinformatics (SIB), 7265 Davos, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7678-7653","authenticated-orcid":false,"given":"Oliver","family":"Schilling","sequence":"additional","affiliation":[{"name":"Institute of Surgical Pathology, Medical Center, University of Freiburg, Breisacher Stra\u00dfe 115a, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.1077209","article-title":"Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism","volume":"299","author":"Bonifati","year":"2003","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1002\/mds.22713","article-title":"DJ-1, PINK1, and their effects on mitochondrial pathways","volume":"25","author":"Cookson","year":"2010","journal-title":"Mov. 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