{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:09:16Z","timestamp":1790698156617,"version":"4.1.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP23K04964"],"award-info":[{"award-number":["JP23K04964"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP26K08567"],"award-info":[{"award-number":["JP26K08567"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K04964"],"award-info":[{"award-number":["JP23K04964"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26K08567"],"award-info":[{"award-number":["JP26K08567"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heme functions as a prosthetic group in numerous hemoproteins, whereas a fraction of intracellular heme is not tightly bound to proteins or membranes and can readily dissociate; this labile heme participates in the regulation of diverse cellular processes. Heme has pro-oxidant properties and is cytotoxic at elevated levels. Accordingly, heme oxygenase-1 (HO-1), an enzyme localized to the endoplasmic reticulum membrane, degrades excess intracellular heme. However, how HO-1 gains access to the excess intracellular heme for degradation remains unclear. In this study, we investigated how the membrane association of HO-1 influences heme capture using a bottom-up approach. A rat HO-1-based fluorescent probe retaining the membrane-anchoring region and capable of detecting heme binding via fluorescence quenching was reconstituted into liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). An HO-1 variant lacking the membrane-anchoring region competitively inhibited heme binding to the probe in the presence of POPC liposomes and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein proposed to function as a heme chaperone. In contrast, membrane-associated HO-1 showed enhanced fluorescence quenching associated with heme binding in the presence of liposomes compared with aqueous conditions, although competition with GAPDH was still observed. These findings suggest that membrane environments may facilitate the access of membrane-associated HO-1 to chaperone-unbound heme under the reconstituted conditions. Our results suggest a model in which membrane localization of HO-1 contributes to the spatial regulation of intracellular heme processing and heme selection for degradation.<\/jats:p>","DOI":"10.1021\/acsomega.6c05685","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:01:49Z","timestamp":1789538509000},"page":"57354-57361","source":"Crossref","is-referenced-by-count":0,"title":["Bottom-Up Model\nSuggesting Membrane Localization of\nHeme Oxygenase-1 Contributes to Heme Selection for Degradation"],"prefix":"10.1021","volume":"11","author":[{"given":"Ryusei","family":"Matsutani","sequence":"first","affiliation":[{"name":"Kyushu Institute of Technology , , ,","place":["Fukuoka, Japan, 820-8502"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Kodama","sequence":"additional","affiliation":[{"name":"Kyushu Institute of Technology , , ,","place":["Fukuoka, Japan, 820-8502"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoichiro","family":"Kusumoto","sequence":"additional","affiliation":[{"name":"Kyushu Institute of Technology , , ,","place":["Fukuoka, Japan, 820-8502"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Sugishima","sequence":"additional","affiliation":[{"name":"Kurume University School of Medicine , , ,","place":["Fukuoka, Japan, 830-0011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Kyushu Institute of Technology , , ,","place":["Fukuoka, Japan, 820-8502"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-865X","authenticated-orcid":true,"given":"Junichi","family":"Taira","sequence":"additional","affiliation":[{"name":"Kyushu Institute of Technology , , ,","place":["Fukuoka, Japan, 820-8502"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"1\u20132","key":"2026092911114991100_cit1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s11010-008-9888-0","article-title":"Differential\nregulation of human ALAS1 mRNA and protein levels by heme and cobalt\nprotoporphyrin","volume":"319","author":"Zheng","year":"2008","journal-title":"Mol. Cell. Biochem"},{"issue":"2","key":"2026092911114991100_cit2","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1093\/jb\/mvh112","article-title":"Role of the heme regulatory\nmotif in the heme-mediated inhibition of mitochondrial import of 5-aminolevulinate\nsynthase","volume":"136","author":"Munakata","year":"2004","journal-title":"J. Biochem"},{"issue":"2","key":"2026092911114991100_cit3","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.molcel.2005.05.027","article-title":"Involvement\nof heme regulatory motif\nin heme-mediated ubiquitination and degradation of IRP2","volume":"19","author":"Ishikawa","year":"2005","journal-title":"Mol. 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Med"},{"issue":"43","key":"2026092911114991100_cit7","doi-asserted-by":"publisher","first-page":"8514","DOI":"10.1021\/bi300863a","article-title":"Heme binding properties of glyceraldehyde-3-phosphate\ndehydrogenase","volume":"51","author":"Hannibal","year":"2012","journal-title":"Biochemistry"},{"key":"2026092911114991100_cit8","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3389\/fphar.2014.00115","article-title":"Heme on innate immunity\nand inflammation","volume":"5","author":"Dutra","year":"2014","journal-title":"Front. Pharmacol"},{"key":"2026092911114991100_cit9","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.freeradbiomed.2015.08.020","article-title":"Heme as\na danger molecule in pathogen\nrecognition","volume":"89","author":"Wegiel","year":"2015","journal-title":"Free Rad. Biol. 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Dispos"},{"key":"2026092911114991100_cit21","doi-asserted-by":"publisher","first-page":"662","DOI":"10.12688\/f1000research.11015.1","article-title":"The catalytic\nfunction of cytochrome P450 is entwined with its membrane-bound nature","volume":"6","author":"Barnaba","year":"2017","journal-title":"F1000res"},{"key":"2026092911114991100_cit22","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jinorgbio.2018.03.002","article-title":"Membrane-attached mammalian cytochromes\nP450: An overview of the membrane\u2019s effects on structure, drug\nbinding, and interactions with redox partners","volume":"183","author":"Srejber","year":"2018","journal-title":"J. Inorg. 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Methods"},{"issue":"1","key":"2026092911114991100_cit29","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.ab.2012.10.002","article-title":"Development\nof a heme sensor using fluorescently labeled heme oxygenase-1","volume":"433","author":"Koga","year":"2013","journal-title":"Anal. Biochem"},{"issue":"27","key":"2026092911114991100_cit30","doi-asserted-by":"publisher","first-page":"7539","DOI":"10.1073\/pnas.1523802113","article-title":"Heme dynamics\nand trafficking factors revealed by genetically encoded fluorescent\nheme sensors","volume":"113","author":"Hanna","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"13","key":"2026092911114991100_cit31","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1021\/acs.biochem.7b00007","article-title":"Heme Gazing: Illuminating Eukaryotic\nHeme Trafficking, Dynamics, and Signaling with Fluorescent Heme Sensors","volume":"56","author":"Hanna","year":"2017","journal-title":"Biochemistry"},{"issue":"11","key":"2026092911114991100_cit32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1615195114","article-title":"Quantification\nof labile heme in live malaria parasites using a genetically encoded\nbiosensor","volume":"114","author":"Abshire","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"37","key":"2026092911114991100_cit33","doi-asserted-by":"publisher","first-page":"14569","DOI":"10.1074\/jbc.H118.005247","article-title":"An unlikely heme chaperone confirmed at last","volume":"293","author":"Fleischhacker","year":"2018","journal-title":"J. Biol. Chem"},{"issue":"37","key":"2026092911114991100_cit34","doi-asserted-by":"publisher","first-page":"14557","DOI":"10.1074\/jbc.RA118.004169","article-title":"Glyceraldehyde-3-phosphate\ndehydrogenase is a chaperone that allocates labile heme in cells","volume":"293","author":"Sweeny","year":"2018","journal-title":"J. Biol. Chem."},{"issue":"28","key":"2026092911114991100_cit35","doi-asserted-by":"publisher","first-page":"20621","DOI":"10.1074\/jbc.M607954200","article-title":"Heme oxygenase-1\nprotein localizes to the nucleus and\nactivates transcription factors important in oxidative stress","volume":"282","author":"Lin","year":"2007","journal-title":"J. Biol. Chem."},{"issue":"18","key":"2026092911114991100_cit36","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.1038\/onc.2014.166","article-title":"Signal peptide peptidase-mediated\nnuclear localization of heme oxygenase-1 promotes cancer cell proliferation\nand invasion independent of its enzymatic activity","volume":"34","author":"Hsu","year":"2015","journal-title":"Oncogene"},{"issue":"1","key":"2026092911114991100_cit37","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3390\/antiox10010087","article-title":"Nuclear\nLocalization of Heme Oxygenase-1 in Pathophysiological\nConditions: Does It Explain the Dual Role in Cancer?","volume":"10","author":"Mascaro","year":"2021","journal-title":"Antioxidants"},{"key":"2026092911114991100_cit38","doi-asserted-by":"publisher","first-page":"102170","DOI":"10.1016\/j.redox.2021.102170","article-title":"The non-canonical\neffects of heme oxygenase-1, a classical fighter against oxidative\nstress","volume":"47","author":"Wu","year":"2021","journal-title":"Redox Biol"},{"issue":"42","key":"2026092911114991100_cit39","doi-asserted-by":"publisher","first-page":"69075","DOI":"10.18632\/oncotarget.11923","article-title":"The non-canonical functions of the\nheme oxygenases","volume":"7","author":"Vanella","year":"2016","journal-title":"Oncotarget"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c05685","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/38\/57354\/68525708\/acsomega.6c05685.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/38\/57354\/68525708\/acsomega.6c05685.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:51:43Z","timestamp":1790697103000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/38\/57354\/5430897\/Bottom-Up-Model-Suggesting-Membrane-Localization"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":39,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,16]]},"published-print":{"date-parts":[[2026,9,29]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c05685","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}