{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:17:06Z","timestamp":1788517026748,"version":"build-2803163510"},"reference-count":67,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004543","name":"Chinese Scholarship Council","doi-asserted-by":"publisher","award":["202208080293"],"award-info":[{"award-number":["202208080293"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Immune cells undergo metabolic reprogramming in response to inflammatory stimuli. The immuneresponsive gene 1 (\n                    <jats:italic>Irg1<\/jats:italic>\n                    ) encodes aconitate decarboxylase (ACOD1), which generates itaconate from\n                    <jats:italic>cis<\/jats:italic>\n                    -aconitate in the TCA cycle. Itaconate inhibits succinate dehydrogenase, resulting in succinate accumulation. Stable ACOD1 overexpression in RAW264.7 cells shifted cellular metabolism towards glycolysis, as indicated by enhanced mTOR activation, increased 4E-BP1 phosphorylation, and reduced ATP levels. ACOD1 cells displayed impaired osteoclastogenesis with reduced expression of osteoclast-associated genes and fewer TRAP-positive multinucleated osteoclasts. Unexpectedly, NFATc1 was constitutively present in the nucleus of untreated ACOD1 cells, resulting in residual NFAT activity and induction of inflammatory genes. Upon RANKL stimulation, these pre-activated cells showed delayed osteoclastogenic signalling accompanied by sustained expression of the transcriptional repressors BCL6, MafB, and IRF8. Using a GPR91 antagonist and a G\u03b1q inhibitor, we demonstrate that extracellular succinate activates NFATc1 via GPR91-G\u03b1q signalling. RNA sequencing further revealed that ACOD1 overexpression promotes an innate immune transcriptional program rather than osteoclast differentiation. Together, our findings identify succinate-GPR91 signalling as a regulator of the transition between inflammatory activation and osteoclastogenesis.\n                  <\/jats:p>","DOI":"10.1515\/hsz-2026-0168","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:59:46Z","timestamp":1788515986000},"source":"Crossref","is-referenced-by-count":0,"title":["ACOD1-dependent succinate signalling acts as a metabolic checkpoint for osteoclast differentiation"],"prefix":"10.1515","author":[{"given":"Yue","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Medical Faculty Heidelberg , Medical Microbiology and Hygiene, Heidelberg University , Im Neuenheimer Feld 324, D-69120 Heidelberg , Germany"},{"name":"Department of Infectious Diseases , University Hospital Heidelberg , Im Neuenheimer Feld 324, D-69120 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genyang","family":"Xin","sequence":"additional","affiliation":[{"name":"School of Medicine , Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University , Shenzhen , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Seebach","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Medical Faculty Heidelberg , Medical Microbiology and Hygiene, Heidelberg University , Im Neuenheimer Feld 324, D-69120 Heidelberg , Germany"},{"name":"Department of Infectious Diseases , University Hospital Heidelberg , Im Neuenheimer Feld 324, D-69120 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Schaack","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology , Heidelberg University Hospital , Im Neuenheimer Feld 420, D-69120 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology , Heidelberg University Hospital , Im Neuenheimer Feld 420, D-69120 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3739-9329","authenticated-orcid":false,"given":"Katharina F.","family":"Kubatzky","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Medical Faculty Heidelberg , Medical Microbiology and Hygiene, Heidelberg University , Im Neuenheimer Feld 324, D-69120 Heidelberg , Germany"},{"name":"Department of Infectious Diseases , University Hospital Heidelberg , Im Neuenheimer Feld 324, D-69120 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026090409594414887_j_hsz-2026-0168_ref_001","doi-asserted-by":"crossref","unstructured":"Alves, C.H., Farrell, E., Vis, M., Colin, E.M., and Lubberts, E. 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