{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:18:29Z","timestamp":1791263909403,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Proteostasis and the regulation of protein folding and sorting play a critical role in maintaining cellular homeostasis. The failure of proteostasis contributes to heart failure and aging, but, despite its importance, the mechanisms and factors regulating proteostasis in cardiomyocytes remain poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Subcellular proteomes of cardiomyocytes were analyzed in vivo using biotin proximity labeling in mouse hearts. We employed a novel homology-independent targeting integration strategy for genetic tagging and for substitution of the muscle-specific skNAC (skeletal nascent polypeptide-associated complex alpha isoform) with the ubiquitous short isoform in cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We identified hundreds of proteins localized to the Z- and M-lines of sarcomeres, the ribosomes, and the desmosomes, including multiple chaperones. A universal homology-independent targeted integration strategy allowed us to genetically tag endogenous genes in the mouse heart and confirm protein localization. We identified the large muscle-specific isoform of the nascent polypeptide-associated complex protein skNAC as a Z-line and ribosome-associated protein. Replacement of skNAC with a ubiquitous isoform induced dilated cardiomyopathy, accompanied by altered ribosome positioning and markedly reduced mitochondrial protein levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>We unraveled the cardiomyocyte subcellular proteome and show that skNAC, an isoform downregulated in disease, is a key ribosome and Z-line-associated protein responsible for cardiomyocyte proteostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.326929","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:00:17Z","timestamp":1765792817000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Subcellular In Vivo Cardiac Proteomics Reveals Sarcomere and Ribosome Interactomes and skNAC\u2019s Impact on Cardiac Proteostasis"],"prefix":"10.1161","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-7954","authenticated-orcid":true,"given":"Rami","family":"Haddad","sequence":"first","affiliation":[{"name":"The Department of Physiology, Biophysics, and Systems Biology, Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology (R.H., O.S., N.S., N.K., I.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Sadeh","sequence":"additional","affiliation":[{"name":"The Department of Physiology, Biophysics, and Systems Biology, Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology (R.H., O.S., N.S., N.K., I.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-7454","authenticated-orcid":true,"given":"Tamar","family":"Ziv","sequence":"additional","affiliation":[{"name":"Smoler Proteomics Center, Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion \u2013 Israel Institute of Technology (T.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-1076","authenticated-orcid":true,"given":"Nardeen","family":"Shehadeh","sequence":"additional","affiliation":[{"name":"The Department of Physiology, Biophysics, and Systems Biology, Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology (R.H., O.S., N.S., N.K., I.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-5325","authenticated-orcid":true,"given":"Nadav","family":"Keren","sequence":"additional","affiliation":[{"name":"The Department of Physiology, Biophysics, and Systems Biology, Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology (R.H., O.S., N.S., N.K., I.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4388-1579","authenticated-orcid":true,"given":"Izhak","family":"Kehat","sequence":"additional","affiliation":[{"name":"The Department of Physiology, Biophysics, and Systems Biology, Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology (R.H., O.S., N.S., N.K., 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