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However, little has been known about how MAM altered in PD. This study was aimed to observe morphological changes and analyze proteomic profiles of MAM in 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\u2010induced PD mouse models. In MPTP\u2010treated mice, transmission electron microscopy was applied for MAM ultrastructural visualization. Nano ultra\u2010high performance liquid chromatography\u2010tandem mass spectrum and bioinformatic analysis were adopted to obtain underlying molecular data of MAM fractions. The loosened, shortened and reduced MAM tethering was found in substantia nigral neurons from MPTP\u2010treated mice. In midbrain MAM proteomics, 158 differentially expressed proteins (DEPs) were identified between two groups. Specific DEPs were validated by western blot and exhibited significantly statistical changes, aligning with proteomic results. Bioinformatic analysis indicated that membrane, cytoplasm and cell projection were three major localizations for DEPs. Biological processes including metabolism, lipid transport, and immunological and apoptotic signaling pathways were greatly affected. For consensus MAM proteins, the enriched pathway analysis revealed the potential relationship between neurodegenerative diseases and MAM. Several biological processes such as peroxisome function and clathrin\u2010mediated endocytosis, were clustered, which provided additional insights into the fundamental molecular pathways associated with MAM. In our study, we demonstrated disrupted ER\u2010mitochondria contacts in an MPTP\u2010induced PD mouse model. The underlying signatures of MAM were revealed by proteomics and bioinformatic analysis, providing valuable insights into its potential role in PD pathogenesis.<\/jats:p>","DOI":"10.1111\/acel.14436","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T07:40:39Z","timestamp":1732952439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The ultrastructural and proteomic analysis of mitochondria\u2010associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-7892","authenticated-orcid":false,"given":"Jin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai People's Republic of 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