{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:26:11Z","timestamp":1760264771935},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,5,4]],"date-time":"2004-05-04T00:00:00Z","timestamp":1083628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,5,4]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>A number of antigens implicated in the pathogenesis of autoimmune diseases including Sjogren's syndrome and systemic lupus erythematosus (SLE) are expressed aberrantly by apoptotic cells. It is also known that apoptogenic proteins are released from the mitochondrial intermembrane space at an early stage during the induction and development of apoptosis. Combination of this evidence led us to test the hypothesis that apoptotic mechanisms provide an explanation for the abnormal expression of the inner mitochondrial enzyme, pyruvate dehydrogenase complex (PDC), observed on the surface of some cells in patients with the autoimmune liver disease primary biliary cirrhosis (PBC). Using one murine and two human cell lines it was found that the induction of apoptosis led to early detection of PDC within the cytoplasm. However, cytochrome c oxidase subunit 4 (COX 4), which is also present on the inner surface of the inner mitochondrial membrane, remained within the mitochondria. Immunoreactive PDC was also detected on the outer surface of the intact plasma membrane of cells sampled after the induction of apoptosis. Serial release of PDC to the cytoplasm and then onto the external surface of the plasma membrane provides direct evidence that the antigen on the cell surface is of mitochondrial origin. Immunoreactivity specific for PDC is strongly implicated in the pathogenesis of PBC, but this autoantigen is normally concealed from the immune system by three membrane systems. Release of PDC onto the cell surface during apoptosis provides a possible route for recognition of this antigen by the immune system which could contribute to both afferent and efferent phases of the disease process.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02484.x","type":"journal-article","created":{"date-parts":[[2004,5,14]],"date-time":"2004-05-14T14:46:12Z","timestamp":1084545972000},"page":"559-567","source":"Crossref","is-referenced-by-count":29,"title":["Apoptosis as a mechanism for cell surface expression of the autoantigen pyruvate dehydrogenase complex"],"prefix":"10.1093","volume":"136","author":[{"given":"P","family":"MACDONALD","sequence":"first","affiliation":[{"name":"Centre for Liver Research and Applied Immunobiology Groups, University of Newcastle, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"PALMER","sequence":"additional","affiliation":[{"name":"Centre for Liver Research and Applied Immunobiology Groups, University of Newcastle, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"KIRBY","sequence":"additional","affiliation":[{"name":"Centre for Liver Research and Applied Immunobiology Groups, University of Newcastle, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D E J","family":"JONES","sequence":"additional","affiliation":[{"name":"Centre for Liver Research and Applied Immunobiology Groups, University of Newcastle, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,5,5]]},"reference":[{"key":"2022011223181963900_b1","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1084\/jem.179.4.1317","article-title":"Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface blebs on cultured keratinocytes","volume":"179","author":"Casciola-Rosen","year":"1994","journal-title":"J Exp Med"},{"key":"2022011223181963900_b2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1046\/j.1365-2184.2002.00239.x","article-title":"Translocation of cytoplasmic HSP70 onto the surface of EL-4 cells duting apoptosis","volume":"35","author":"Sapozhnikov","year":"2002","journal-title":"Cell Prolif"},{"key":"2022011223181963900_b3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0889-857X(05)70136-8","article-title":"Apoptosis in systemic lupus erythematosis. 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