{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:26:33Z","timestamp":1793582793188,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microscopy Res &amp; Technique"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sonic Hedgehog\u2010activated medulloblastomas (SHH\u2010MBs) are aggressive, heterogeneous embryonal neuroepithelial tumors predominantly occurring in the pediatric posterior fossa. Postoperative recurrence and metastasis closely associate with aberrant mitochondrial subcellular localization and dysfunctional mitochondrial quality control. Mitophagy, the selective autophagic degradation of damaged or superfluous mitochondria, is intricately regulated by the PINK1\u2010Parkin signaling pathway in metazoan cells. Nevertheless, the biological significance and the regulatory mechanisms underlying Sonic Hedgehog\u2010mediated medulloblastoma (SHH\u2010MB) proliferation, invasion, metastasis, and recurrence are not yet fully elucidated. In this study, integrated molecular and microscopy\u2010based analyses revealed that PINK1 mRNA and protein levels were significantly downregulated in primary human SHH\u2010MB specimens versus adjacent non\u2010tumor brain tissues, as well as in a panel of SHH\u2010MB cell lines. Transmission electron microscopy (TEM) directly visualized impaired mitophagic flux, fragmented mitochondrial morphology, and accumulated damaged mitochondria in PINK1\u2010deficient SHH\u2010MB cells. In\u00a0vitro functional assays showed that PINK1 overexpression minimally affected apoptosis but markedly suppressed cell proliferation, migration, and invasion, and potently restored mitophagic activity as validated by mitochondrial autophagy imaging. Combined RNA\u2010sequencing, KEGG pathway enrichment, and Western blot verification further demonstrated that PINK1 depletion was associated with hyperactivation of the PI3K\/AKT signaling cascade. Collectively, our microscopy\u2010supported mechanistic data demonstrate that PINK1 downregulation inhibits mitophagy in SHH\u2010MB, an effect associated with sustained PI3K\/AKT pathway activation. These findings highlight PINK1 as a promising diagnostic biomarker and potential therapeutic target for SHH\u2010driven medulloblastoma, although the precise mechanistic relationship between PINK1 and PI3K\/AKT signaling requires further investigation.<\/jats:p>","DOI":"10.1002\/jemt.70192","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:25:06Z","timestamp":1792045506000},"page":"1371-1385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low Expression of\n                    <scp>PINK1<\/scp>\n                    Suppresses Mitophagy in Sonic Hedgehog\u2013Driven Medulloblastoma in Association With Activation of the\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Signaling Pathway"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-1555","authenticated-orcid":false,"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ultrastructural Pathology, Neuropathology Center Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Core Facilities Center Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9944-2157","authenticated-orcid":false,"given":"Chao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Beijing Luhe Hospital, Capital Medical University  Beijing 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