{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:18:09Z","timestamp":1783423089290,"version":"3.54.6"},"reference-count":36,"publisher":"IMR Press","issue":"6","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC3500502"],"award-info":[{"award-number":["2022YFC3500502"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Anhui Provincial Scientific Research Planning Project","award":["2023AH050796"],"award-info":[{"award-number":["2023AH050796"]}]},{"name":"University talent support program","award":["2023rcyb002"],"award-info":[{"award-number":["2023rcyb002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Heart failure (HF) is characterized by mitochondrial dysfunction and immune dysregulation. However, the underlying molecular mechanisms remain unclear. Functional enrichment analyses study aimed to identify key mitochondrial genes involved in HF pathogenesis and to explore their association with immune cell infiltration.Methods:Differentially expressed genes related to HF were identified and subjected to functional enrichment analyses. Summary data-based Mendelian randomization (SMR) was used to evaluate the diagnostic potential of candidate genes. Immune cell infiltration analysis was performed to assess associations between gene expression and immune profiles. Single-cell RNA sequencing data (GSE145154) were analyzed to determine cell-specific expression patterns. A transverse aortic constriction (TAC)-induced HF mouse model was established, and cardiac function was assessed by echocardiography. Histopathological analyses were conducted to evaluate myocardial injury, fibrosis, and apoptosis. Immune cell populations were further examined in vivo.Results:Functional enrichment analysis revealed that HF-related genes were significantly associated with mitochondrial organization and pathways such as mechanistic target of rapamycin (mTOR) signaling and cardiomyopathy. SMR analysis identified NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) and NME\/NM23 nucleoside diphosphate kinase 6 (NME6) as having diagnostic relevance. Immune infiltration analysis showed correlations between these genes and immune cell populations. Single-cell RNA sequencing revealed that NME6 was predominantly expressed in T cells and neutrophils, indicating potentially important significance. Clinical data suggested that brain natriuretic peptide (BNP), C-reactive protein (CRP), neutrophils, monocytes, and inflammatory factor levels tended to increase with HF severity. Echocardiography determined that in HF mice, NME6 knockdown lessened the left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) while boosting the left ventricular ejection fraction (LVEF) and fractional shortening (LVFS). Histopathological analysis further demonstrated that NME6 knockdown alleviated myocardial damage and fibrosis, and inhibited cardiomyocyte apoptosis in HF mice. In-depth studies indicated that NME6 knockdown mitigated HF by increasing the proportion of CD4+ T cells and decreasing the proportions of CD8+ T cells and CD44+CD62L+ T cells.Conclusions:NME6 may act as a regulator of immune responses and a potential therapeutic target in HF, providing new insights into the molecular mechanisms of HF.<\/jats:p>","DOI":"10.31083\/fbl48958","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:50:51Z","timestamp":1783421451000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of the Mitochondrial Gene NME6 as an Immune Modulator in Heart Failure"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-0323","authenticated-orcid":true,"given":"Pan","family":"Liu","sequence":"first","affiliation":[{"name":"Zhongyi School, Anhui University of Chinese Medicine, 230012 Hefei, Anhui, China"},{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230013 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8969-6946","authenticated-orcid":true,"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230013 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6952-816X","authenticated-orcid":true,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory, The Third People\u2019s Hospital of Bengbu Affiliated to Bengbu Medical University (Bengbu Central Hospital), 233099 Bengbu, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7850-0657","authenticated-orcid":true,"given":"Jingjing","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230013 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4040-3944","authenticated-orcid":true,"given":"Xianwei","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230013 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9934-6033","authenticated-orcid":true,"given":"Liang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230013 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8165-8917","authenticated-orcid":true,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhongyi School, Anhui University of Chinese Medicine, 230012 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5261-7107","authenticated-orcid":true,"given":"Xiaoyu","family":"Qiang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Science, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6251-8778","authenticated-orcid":true,"given":"Shiguang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, 230013 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-3777","authenticated-orcid":true,"given":"Ran","family":"Xia","sequence":"additional","affiliation":[{"name":"Zhongyi School, Anhui University of Chinese Medicine, 230012 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Ranek M, Berthiaume J, Kirk J, Lyon R, Sheikh F, Jensen B, et al. 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