{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:20Z","timestamp":1787027720191,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean National Research Foundation of Republic of Korea (NRF)","award":["NRF-2023R1A2C1005720"],"award-info":[{"award-number":["NRF-2023R1A2C1005720"]}]},{"name":"Korean National Research Foundation of Republic of Korea (NRF)","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"name":"Korean National Research Foundation of Republic of Korea (NRF)","award":["NSFC31860288"],"award-info":[{"award-number":["NSFC31860288"]}]},{"name":"Republic of Korean Hypertension Society","award":["NRF-2023R1A2C1005720"],"award-info":[{"award-number":["NRF-2023R1A2C1005720"]}]},{"name":"Republic of Korean Hypertension Society","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"name":"Republic of Korean Hypertension Society","award":["NSFC31860288"],"award-info":[{"award-number":["NSFC31860288"]}]},{"name":"National Natural Science Foundation of China","award":["NRF-2023R1A2C1005720"],"award-info":[{"award-number":["NRF-2023R1A2C1005720"]}]},{"name":"National Natural Science Foundation of China","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"name":"National Natural Science Foundation of China","award":["NSFC31860288"],"award-info":[{"award-number":["NSFC31860288"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hydrogen sulfide (H2S) has been established to regulate mitochondrial respiration and ATP production, but whether the regulation is through S-sulfhydration (-SSH) of mitochondrial complexes is not well understood. Recently, H2S is known to exert diverse and dose-dependent effects on mitochondrial complexes. However, the involvement of S-sulfhydration of each mitochondrial complex and the activities in diabetic hearts have not been revealed. Here, we conducted comprehensive investigations into S-sulfhydration and the activities of mitochondrial complexes I\u2013V in normal and Streptozotocin (STZ)-induced type 1 diabetic (DM) heart mitochondria. Results showed that proteins of H2S-producing enzymes were downregulated in DM heart mitochondria, which was accompanied by reduced mitochondrial membrane potential (MMP), greater ROS, and lower complex I and V activities, reduced complex V-SSH in DM. In both groups, supplementation with the H2S donor NaHS increased the S-sulfhydration of all mitochondrial complexes, and the activities of complexes I\u2013III and V were significantly increased but complex IV activity was reduced. Consequently, mitochondrial MMP, ROS, and ATP production were normalized with NaHS in DM, whereas inhibition of H2S generation increased mitochondrial ROS and reduced MMP via reducing complex activities in both groups. Ischemic reperfusion did not affect NaHS-increment of S-sulfhydration of complexes I\u2013V, but significantly impaired complex V activity in DM. Collectively, H2S-dependent S-sulfhydration of mitochondrial complexes I\u2013V in normal and DM heart mitochondria were involved in the activation of mitochondrial complexes I\u2013III\/V and the inhibition of complex IV, which control cardiac mitochondrial respiration and ATP production.<\/jats:p>","DOI":"10.3390\/biom15081197","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dual Regulation of Mitochondrial Complexes by H2S via S-Sulfhydration Controls Respiration in Type 1 Diabetic Hearts"],"prefix":"10.3390","volume":"15","author":[{"given":"Tong","family":"Su","sequence":"first","affiliation":[{"name":"Yanbian University College of Medicine, Yanbian University Hospital, Yanji 133000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Han","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8303-8132","authenticated-orcid":false,"given":"Jun Xian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Yuan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biomedical Sciences, Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixing","family":"Cui","sequence":"additional","affiliation":[{"name":"Yanbian University College of Medicine, Yanbian University Hospital, Yanji 133000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7810-1970","authenticated-orcid":false,"given":"Longhao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-0134","authenticated-orcid":false,"given":"Yin Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yanbian University College of Medicine, Yanbian University Hospital, Yanji 133000, China"},{"name":"Department of Physiology & Biomedical Sciences, Ischemic\/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1126\/science.abd8377","article-title":"Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance","volume":"372","author":"Shatalin","year":"2021","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Peleli, M., Bibli, S.I., Li, Z., Chatzianastasiou, A., Varela, A., Katsouda, A., Zukunft, S., Bucci, M., Vellecco, V., and Davos, C.H. 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