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Although genomic studies have identified loci associated with thermoregulatory traits, sequence variation alone does not explain the rapid, reversible cellular adaptations required during acute thermal challenge. Increasing evidence suggests that thermotolerance depends on coordinated regulation between nuclear transcriptional architecture and mitochondrial metabolic stability. This review synthesizes mechanistic insights into two interconnected regulatory axes: heat shock factor 1 (HSF1)\u2013dependent nuclear stress body (nSB) formation and mitochondrial\u2013nuclear signaling. During thermal exposure, HSF1 reorganizes chromatin through phase\u2010separated nuclear condensates, amplifying stress\u2010inducible transcription. Concurrently, mitochondrial perturbation alters reactive oxygen species production, calcium flux, and ATP availability, thereby influencing chromatin accessibility and transcription factor activity. Experimental studies in mammalian systems demonstrate that oxidative signaling modulates HSF1 DNA\u2010binding competence, while mitochondrial metabolites regulate histone acetylation and demethylation, linking energetic status to transcriptional plasticity. These cross\u2010compartmental processes determine whether cells maintain proteostasis and recover or progress toward apoptotic and inflammatory outcomes. Although direct characterization in cattle remains limited, breed\u2010level differences in heat shock protein induction, mitochondrial ROS handling, and mtDNA haplotypes suggest meaningful variation in regulatory resilience. The efficiency of coordination between nuclear activation and mitochondrial stabilization may therefore represent a critical determinant of thermotolerance. We further frame thermotolerance as a resource\u2010allocation trait, reflecting energetic partitioning among milk synthesis, immune function, reproduction, and stress protection in high\u2010producing dairy cattle. Understanding these cross\u2010compartmental regulatory mechanisms may support future studies identifying biomarkers and genomic targets for improving heat resilience in cattle.<\/jats:p>","DOI":"10.1002\/age.70169","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:12:24Z","timestamp":1784877144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nuclear Stress Bodies and Mitochondrial Signal Transduction Regulate Thermotolerance in Cattle: Insights Into Molecular Mechanisms"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7676-9475","authenticated-orcid":false,"given":"David Olusola","family":"Aderibigbe","sequence":"first","affiliation":[{"name":"Animal Breeding and Genetics Units, Department of Animal Science, Faculty of Agriculture University of Ibadan  Ibadan Nigeria"},{"name":"Institute of Animal Sciences (IAS) Chinese Academy of Agricultural Sciences (CAAS)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4910-151X","authenticated-orcid":false,"given":"Jesse Oluwaseun","family":"Ayantoye","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genetics Units, Department of Animal Science, Faculty of Agriculture University of Ibadan  Ibadan Nigeria"},{"name":"Institute of Animal Sciences (IAS) Chinese Academy of Agricultural Sciences (CAAS)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9934-1862","authenticated-orcid":false,"given":"Obianwuna Uchechukwu","family":"Edna","sequence":"additional","affiliation":[{"name":"Laboratory of Quality &amp; Safety Risk Assessment for Animal Products on Feed Hazards (Beijing) of the Ministry of Agriculture &amp; Rural Affairs Institute of Feed Research, Chinese Academy of Agricultural Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1788-1572","authenticated-orcid":false,"given":"Osamede Henry","family":"Osaiyuwu","sequence":"additional","affiliation":[{"name":"Animal Breeding and Genetics Units, Department of Animal Science, Faculty of Agriculture University of Ibadan  Ibadan Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005753"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1044503"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010021\u201002489\u20107"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.06.061"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biochem\u2010060809\u2010095203"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.001"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010animal\u2010031412\u2010103644"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2019\u201017929"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2013\u20106611"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2015"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2024\u201025203"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110162"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14590"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani12243585"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2015\u201010212"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.007"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13981"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fanim.2022.852958"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11626\u2010020\u201000446\u20105"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2024.1405263"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.034"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2015.05.007"},{"key":"e_1_2_14_24_1","unstructured":"Collier R. 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