{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:29:46Z","timestamp":1790886586160,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"Kavli Institute for Neuroscience at Yale and the National Institutes of Health NIDA","doi-asserted-by":"publisher","award":["DA023999"],"award-info":[{"award-number":["DA023999"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial malfunction and morphologic disorganization have been observed in brain cells as part of complex pathological changes. However, it is unclear what may be the role of mitochondria in the initiation of pathologic processes or if mitochondrial disorders are consequences of earlier events. We analyzed the morphologic reorganization of organelles in an embryonic mouse brain during acute anoxia using an immunohistochemical identification of the disordered mitochondria, followed by electron microscopic three-dimensional (3D) reconstruction. We found swelling of the mitochondrial matrix after 3 h anoxia and probable dissociation of mitochondrial stomatin-like protein 2 (SLP2)-containing complexes after 4.5 h anoxia in the neocortex, hippocampus, and lateral ganglionic eminence. Surprisingly, deformation of the Golgi apparatus (GA) was detected already after 1 h of anoxia, when the mitochondria and other organelles still had a normal ultrastructure. The disordered GA showed concentrical swirling of the cisternae and formed spherical onion-like structures with the trans-cisterna in the center of the sphere. Such disturbance of the Golgi architecture likely interferes with its function for post-translational protein modification and secretory trafficking. Thus, the GA in embryonic mouse brain cells may be more vulnerable to anoxic conditions than the other organelles, including mitochondria.<\/jats:p>","DOI":"10.3390\/ijms24054432","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T02:32:12Z","timestamp":1677205932000},"page":"4432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Disorder of Golgi Apparatus Precedes Anoxia-Induced Pathology of Mitochondria"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3679-6819","authenticated-orcid":false,"given":"Yury M.","family":"Morozov","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Kavli Institute for Neuroscience, Yale School of Medicine, Yale University, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasko","family":"Rakic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Kavli Institute for Neuroscience, Yale School of Medicine, Yale University, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1073\/pnas.1311310110","article-title":"Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment","volume":"111","author":"Hara","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1126\/science.1219855","article-title":"Mitochondrial fission, fusion, and stress","volume":"337","author":"Youle","year":"2012","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tem.2015.12.001","article-title":"Mitochondrial Dynamics and Metabolic Regulation","volume":"27","author":"Wai","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41580-020-0210-7","article-title":"The cell biology of mitochondrial membrane dynamics","volume":"21","author":"Giacomello","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature12985","article-title":"Mitochondrial form and function","volume":"505","author":"Friedman","year":"2014","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7494863","DOI":"10.1155\/2022\/7494863","article-title":"Prohibitins: A Key Link between Mitochondria and Nervous System Diseases","volume":"2022","author":"Jiang","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/ejn.13124","article-title":"Alteration of SLP2-like immunolabeling in mitochondria signifies early cellular damage in developing and adult mouse brain","volume":"43","author":"Morozov","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1161\/hs0302.104541","article-title":"Ultrastructural changes of neuronal mitochondria after transient and permanent cerebral ischemia","volume":"33","author":"Solenski","year":"2002","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1093\/cercor\/bhaa134","article-title":"Rapid Neuronal Ultrastructure Disruption and Recovery during Spreading Depolarization-Induced Cytotoxic Edema","volume":"30","author":"Kirov","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nbd.2015.10.011","article-title":"Mitochondrial fusion\/fission dynamics in neurodegeneration and neuronal plasticity","volume":"90","author":"Bertholet","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s12035-014-8893-4","article-title":"The Impact of Mitochondrial Fusion and Fission Modulation in Sporadic Parkinson\u2019s Disease","volume":"52","author":"Santos","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9090","DOI":"10.1523\/JNEUROSCI.1357-09.2009","article-title":"Impaired balance of mitochondrial fission and fusion in Alzheimer\u2019s disease","volume":"29","author":"Wang","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18725","DOI":"10.1038\/srep18725","article-title":"Altered brain energetics induces mitochondrial fission arrest in Alzheimer\u2019s Disease","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1523\/JNEUROSCI.1510-16.2016","article-title":"Reversible Disruption of Neuronal Mitochondria by Ischemic and Traumatic Injury Revealed by Quantitative Two-Photon Imaging in the Neocortex of Anesthetized Mice","volume":"37","author":"Kislin","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neurobiolaging.2016.12.001","article-title":"Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex","volume":"51","author":"Morozov","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e461","DOI":"10.1038\/cddis.2012.213","article-title":"Computational classification of mitochondrial shapes reflects stress and redox state","volume":"4","author":"Ahmad","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.tice.2016.12.002","article-title":"Different Golgi ultrastructure across species and tissues: Implications under functional and pathological conditions, and an attempt at classification","volume":"49","author":"Mironov","year":"2017","journal-title":"Tissue Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/ar.1092420302","article-title":"Trans-Golgi network (TGN) of different cell types: Three-dimensional structural characteristics and variability","volume":"242","author":"Clermont","year":"1995","journal-title":"Anat. Rec."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.21767\/2471-8084.100006","article-title":"Onco-Golgi: Is Fragmentation a Gate to Cancer Progression?","volume":"1","author":"Petrosyan","year":"2015","journal-title":"Biochem. Mol. Biol. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S153","DOI":"10.3233\/JAD-132660","article-title":"Golgi apparatus and protein trafficking in Alzheimer\u2019s disease","volume":"42","author":"Baloyannis","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1177\/1533317514556876","article-title":"The hypothalamus in Alzheimer\u2019s disease: A Golgi and electron microscope study","volume":"30","author":"Baloyannis","year":"2015","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Dement."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.neurobiolaging.2013.11.022","article-title":"Golgin-84-associated Golgi fragmentation triggers tau hyperphosphorylation by activation of cyclin-dependent kinase-5 and extracellular signal-regulated kinase","volume":"35","author":"Jiang","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10662","DOI":"10.1523\/JNEUROSCI.23-33-10662.2003","article-title":"Reduction of detyrosinated microtubules and Golgi fragmentation are linked to tau-induced degeneration in astrocytes","volume":"23","author":"Yoshiyama","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/S0002-9440(10)62366-8","article-title":"Fragmentation of the Golgi apparatus induced by the overexpression of wild-type and mutant human tau forms in neurons","volume":"166","author":"Liazoghli","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1007\/s11064-021-03296-z","article-title":"Radial Glial Cells: New Views on Old Questions","volume":"46","author":"Arellano","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Morozov, Y.M., Mackie, K., and Rakic, P. (2020). Cannabinoid Type 1 Receptor is Undetectable in Rodent and Primate Cerebral Neural Stem Cells but Participates in Radial Neuronal Migration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228657"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1111\/ejn.12237","article-title":"Antibodies to cannabinoid type 1 receptor co-react with stomatin-like protein 2 in mouse brain mitochondria","volume":"38","author":"Morozov","year":"2013","journal-title":"Eur. J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bouybayoune, I., Mantovani, S., Del Gallo, F., Bertani, I., Restelli, E., Comerio, L., Tapella, L., Baracchi, F., Fern\u00e1ndez-Borges, N., and Mangieri, M. (2015). Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004796"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_30","first-page":"38","article-title":"Effects of Brefeldin A on the Golgi complex, endoplasmic reticulum and viral envelope glycoproteins in murine erythroleukemia cells","volume":"54","author":"Ulmer","year":"1991","journal-title":"Eur. J. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ar.1092410102","article-title":"Effects of brefeldin A on the three-dimensional structure of the Golgi apparatus in a sensitive strain of Saccharomyces cerevisiae","volume":"241","author":"Rambourg","year":"1995","journal-title":"Anat. Rec."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Han, S., Nandy, P., Austria, Q., Siedlak, S.L., Torres, S., Fujioka, H., Wang, W., and Zhu, X. (2020). Mfn2 Ablation in the Adult Mouse Hippocampus and Cortex Causes Neuronal Death. Cells, 9.","DOI":"10.3390\/cells9010116"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1523\/JNEUROSCI.2324-19.2020","article-title":"Neuronal Mitochondria Modulation of LPS-Induced Neuroinflammation","volume":"40","author":"Harland","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.molmet.2017.01.004","article-title":"Cannabinoid type 1 receptor-containing axons innervate NPY\/AgRP neurons in the mouse arcuate nucleus","volume":"6","author":"Morozov","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1128\/MCB.05393-11","article-title":"Stomatin-like protein 2 binds cardiolipin and regulates mitochondrial biogenesis and function","volume":"31","author":"Christie","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mitsopoulos, P., Lapohos, O., Weraarpachai, W., Antonicka, H., Chang, Y.H., and Madrenas, J. (2017). Stomatin-like protein 2 deficiency results in impaired mitochondrial translation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179967"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.hlc.2021.05.074","article-title":"Stomatin-Like Protein-2: A Potential Target to Treat Mitochondrial Cardiomyopathy","volume":"30","author":"Hu","year":"2021","journal-title":"Heart Lung Circ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.bbamcr.2008.02.006","article-title":"SLP-2 interacts with prohibitins in the mitochondrial inner membrane and contributes to their stability","volume":"1783","author":"Parone","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.15252\/embr.201642698","article-title":"The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L","volume":"17","author":"Wai","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1365-2818.2005.01466.x","article-title":"Reconstruct: A free editor for serial section microscopy","volume":"218","author":"Fiala","year":"2005","journal-title":"J. Microsc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jamia.2001.0080001","article-title":"Extending unbiased stereology of brain ultrastructure to three-dimensional volumes","volume":"8","author":"Fiala","year":"2001","journal-title":"J. Am. Med. Inform. Assoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4432\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:40:32Z","timestamp":1760121632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,23]]},"references-count":41,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054432"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054432","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,23]]}}}