{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:39Z","timestamp":1792788759718,"version":"4.5.0"},"reference-count":60,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,22]]},"abstract":"<jats:p>\n                    Defects in endoplasmic reticulum (ER) proteostasis have been linked to diseases in multiple organ systems. Here we examined the impact of perturbation of ER proteostasis in mice bearing thyrocyte-specific knockout of either\n                    <jats:italic>HRD1<\/jats:italic>\n                    (to disable ER-associated protein degradation [ERAD]) or\n                    <jats:italic>ATG7<\/jats:italic>\n                    (to disable autophagy) in the absence or presence of heterozygous expression of misfolded mutant thyroglobulin (the most highly expressed thyroid gene product, synthesized in the ER). Misfolding-inducing thyroglobulin mutations are common in humans but are said to yield only autosomal-recessive disease \u2014 perhaps because misfolded thyroglobulin protein might undergo disposal by ERAD or ER macroautophagy. We find that as single defects, neither ERAD, nor autophagy, nor heterozygous thyroglobulin misfolding altered circulating thyroxine levels, and neither defective ERAD nor defective autophagy caused any gross morphological change in an otherwise WT thyroid gland. However, heterozygous expression of misfolded thyroglobulin itself triggered significant ER stress and individual thyrocyte death while maintaining integrity of the surrounding thyroid epithelium. In this context, deficiency of ERAD (but not autophagy) resulted in patchy whole-follicle death with follicular collapse and degeneration, accompanied by infiltration of bone marrow\u2013derived macrophages. Perturbation of thyrocyte ER proteostasis is thus a risk factor for both cell death and follicular demise.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.169937","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T14:05:15Z","timestamp":1687356315000},"source":"Crossref","is-referenced-by-count":17,"title":["Perturbation of endoplasmic reticulum proteostasis triggers tissue injury in the thyroid gland"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-6904","authenticated-orcid":true,"given":"Xiaohan","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Metabolism, Endocrinology & Diabetes and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1538-8733","authenticated-orcid":true,"given":"Crystal","family":"Young","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology & Diabetes and"},{"name":"Department of 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