{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:29:35Z","timestamp":1777868975054,"version":"3.51.4"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":119,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis\u2010induced acute lung injury (SI\u2010ALI) is a major cause of morbidity and mortality among septic patients. Recent evidence highlights the role of mitochondria\u2010associated membranes (MAMs)\u2014specialized contact sites between the endoplasmic reticulum (ER) and mitochondria\u2014in regulating calcium signaling, lipid metabolism, energy homeostasis, and immune responses. Structural and functional alterations of MAMs are increasingly recognized as critical contributors to the pathogenesis of SI\u2010ALI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This review aims to summarize the structural and functional characteristics of MAMs, elucidate their alterations and immunoregulatory roles in sepsis\u2010induced lung injury, and discuss potential therapeutic strategies targeting MAMs to mitigate pulmonary damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive literature review was conducted using recent studies focused on the molecular structure, signaling mechanisms, and pathological changes of MAMs in sepsis and related inflammatory diseases. Emphasis was placed on calcium signaling, mitochondrial dysfunction, oxidative stress, and inflammasome activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MAMs maintain close ER\u2013mitochondria contacts (10\u201330\u2009nm) through key proteins such as inositol 1,4,5\u2010trisphosphate receptor (IP3R), glucose\u2010regulated protein 75 (GRP75), voltage\u2010dependent anion channel (VDAC), and mitofusin\u20102 (MFN2). During sepsis, oxidative stress and inflammatory cytokines disrupt these contacts, leading to impaired calcium transfer, mitochondrial dysfunction, and energy deficiency. Dysregulated MAMs promote NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, excessive reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) release, thereby amplifying inflammatory cascades and immune cell apoptosis. Therapeutic strategies that restore MAM integrity\u2014such as upregulating MFN2, activating ER autophagy, or modulating calcium transport proteins\u2014have shown potential to attenuate lung injury by improving mitochondrial metabolism and reducing oxidative stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MAMs play essential roles in maintaining intracellular homeostasis and immune balance. Their structural and functional disruption contributes significantly to the progression of SI\u2010ALI. Targeting MAMs offers promising therapeutic opportunities for preventing and treating sepsis\u2010induced lung injury, although further mechanistic and clinical studies are warranted to translate these findings into practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jimr\/9888339","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:58:31Z","timestamp":1777553911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural and Functional Alterations of MAMs and Their Immunomodulatory Roles in Sepsis\u2010Induced Lung Injury"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3260-2986","authenticated-orcid":false,"given":"Yihao","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9996-6537","authenticated-orcid":false,"given":"Jingran","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2471-3561","authenticated-orcid":false,"given":"Xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.52"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101920"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1389202"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107409"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2024.153979"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.796061"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115011"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.09.003"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13010005"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156952"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2024.101874"},{"key":"e_1_2_13_12_2","doi-asserted-by":"crossref","unstructured":"HartS. 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