{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T21:50:01Z","timestamp":1779400201919,"version":"3.53.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Prostatic diseases, consisting of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa), pose significant health challenges. While single-omics studies have provided valuable insights into the role of mitochondrial dysfunction in prostatic diseases, integrating multi-omics approaches is essential for uncovering disease mechanisms and identifying therapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A genome-wide meta-analysis was conducted for prostatic diseases using the genome-wide association studies (GWAS) data from FinnGen and UK Biobank. Mitochondrial dysfunction-related genes were reviewed based on MitoCarta 3.0, with a library containing 1,244 mitochondrial genes. We integrated multi-omics through quantitative trait loci (QTL) across gene expression (eQTLs), protein abundance (pQTLs), and DNA methylation (mQTLs). We prioritized prostatic disease-related mitochondrial genes into three confidence tiers: Tier 1 (two eQTLs + pQTL + mQTL); Tier 2 (two eQTLs + pQTL\/mQTL); and Tier 3 (eQTL + pQTL\/mQTL). Further mediation analyses were performed to explore potential mediating pathways for the interaction between mitochondrial dysfunction and prostatic diseases, with 1,400 metabolomics and 731 immunomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified DCXR as the gene with Tier 1 evidence for BPH, validated by multi-omics integration through transcriptomic, proteomic, and methylomic signatures. We revealed two Tier 2 genes (NOA1 and ELAC2) and one Tier 3 gene (ACAT1) for BPH, two Tier 3 genes (TRMU and SFXN5) for prostatitis, and six Tier 3 genes (MRPL24, NDUFS6, PUS1, NBR1, GLOD4, and PCBD2) for PCa. We also explored the mediating pathways of mitochondrial genes (within the 3-tiers evidence) on prostatic diseases, and identified 8, 4, and 13 metabolites mediating the interaction between mitochondrial genes and BPH, prostatitis, and PCa, respectively, without the involvement of immune characters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings highlight the roles of mitochondrial dysfunction-related genes in prostatic diseases and identify key genes and pathways for potential therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1609933","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T04:11:04Z","timestamp":1755835864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics"],"prefix":"10.3389","volume":"16","author":[{"given":"Binbin","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianrui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhao","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nature24277","article-title":"Genetic effects on gene expression across human tissues","volume":"550","author":"Battle","year":"2017","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/s41419-024-06893-2","article-title":"Targeting valine catabolism to inhibit metabolic reprogramming in prostate cancer","volume":"15","author":"Bidgood","year":"2024","journal-title":"Cell Death & Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"112217","DOI":"10.1016\/j.biopha.2021.112217","article-title":"Urinary metabolomics of HCV patients with severe liver fibrosis before and during the sustained virologic response achieved by direct acting antiviral treatment","volume":"143","author":"Biliotti","year":"2021","journal-title":"Biomed. & Pharmacother. = Biomedecine & Pharmacother."},{"key":"B4","doi-asserted-by":"publisher","first-page":"13728","DOI":"10.1073\/pnas.1107898108","article-title":"Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer","volume":"108","author":"Chang","year":"2011","journal-title":"Proc. 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