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Despite its severity, the intrinsic factors governing cardiomyocyte damage in DCM remain unclear. It is hypothesized that impaired iron\u2013sulfur (Fe\u2013S) cluster synthesis plays a crucial role in the pathogenesis of DCM. Reduced S\u2010sulfhydration of cysteine desulfurase (NFS1) is a novel mechanism that contributes to mitochondrial dysfunction and PARthanatos in DCM. Mechanistically, hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) supplementation restores NFS1 S\u2010sulfhydration at cysteine 383 residue, thereby enhancing Fe\u2013S cluster synthesis, improving mitochondrial function, increasing cardiomyocyte viability, and alleviating cardiac damage. This study provides novel insights into the interplay between Fe\u2013S clusters, mitochondrial dysfunction, and PARthanatos, highlighting a promising therapeutic target for DCM and paving the way for potential clinical interventions to improve patient outcomes.\n                  <\/jats:p>","DOI":"10.1002\/advs.202406695","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T12:40:27Z","timestamp":1730724027000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Impaired Iron\u2013Sulfur Cluster Synthesis Induces Mitochondrial PARthanatos in Diabetic Cardiomyopathy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9348-6876","authenticated-orcid":false,"given":"Mengyi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Harbin Medical University  No. 246 Xuefu ROAD Harbin 150086 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