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We have discovered that hydrogen sulfide, a signaling metabolite generated in copious quantities at the host-microbiome interface, upregulates Cu accumulation in diffusely dispersed puncta across the cell, as visualized by X-ray fluorescence microscopy. The Cu is predominantly in the Cu\n                  <jats:sup>2+<\/jats:sup>\n                  state with oxygen\/nitrogen ligands. Cu import occurs via the non- canonical ZNT1 transporter, while export, following sulfide withdrawal, is ATP7A-dependent. Cu accumulates at the apices of colon crypts in a mouse model of elevated sulfide exposure due to SQOR deficiency in the intestinal epithelium, establishing\n                  <jats:italic>in vivo<\/jats:italic>\n                  relevance. Our study reveals that sulfide is a dynamic regulator of the Cu pool, stimulating Cu\n                  <jats:sup>2+<\/jats:sup>\n                  influx into highly concentrated puncta.\n                <\/jats:p>","DOI":"10.64898\/2026.07.30.741779","type":"posted-content","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:08:33Z","timestamp":1785719313000},"source":"Crossref","is-referenced-by-count":0,"title":["Hydrogen sulfide dynamically upregulates copper uptake and localization"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4044-5413","authenticated-orcid":false,"given":"Jutta","family":"Diessl","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, 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