{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:14:53Z","timestamp":1791220493156,"version":"4.1.0"},"reference-count":51,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["1R21NS101652-01"],"award-info":[{"award-number":["1R21NS101652-01"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["R01 NS065874"],"award-info":[{"award-number":["R01 NS065874"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","doi-asserted-by":"publisher","award":["P41GM103412"],"award-info":[{"award-number":["P41GM103412"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:p> Patients with chronic mountain sickness (CMS) suffer from hypoxemia, erythrocytosis, and numerous neurologic deficits. Here we used induced pluripotent stem cell (iPSC)-derived neurons from both CMS and non-CMS subjects to study CMS neuropathology. Using transmission electron microscopy, we report that CMS neurons have a decreased mitochondrial volume density, length, and less cristae membrane surface area. Real-time PCR confirmed a decreased mitochondrial fusion gene optic atrophy 1 (OPA1) expression. Immunoblot analysis showed an accumulation of the short isoform of OPA1 (S-OPA1) in CMS neurons, which have reduced ATP levels under normoxia and increased lactate dehydrogenase (LDH) release and caspase 3 activation after hypoxia. Improving the balance between the long isoform of OPA1 and S-OPA1 in CMS neurons increased the ATP levels and attenuated LDH release under hypoxia. Our data provide initial evidence for altered mitochondrial morphology and function in CMS neurons, and reveal increased cell death under hypoxia due in part to altered mitochondrial dynamics. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Induced pluripotent stem cell-derived neurons from chronic mountain sickness (CMS) subjects have altered mitochondrial morphology and dynamics, and increased sensitivity to hypoxic stress. Modification of OPA1 can attenuate cell death after hypoxic treatment, providing evidence that altered mitochondrial dynamics play an important role in increased vulnerability under stress in CMS neurons. <\/jats:p>","DOI":"10.1152\/japplphysiol.00689.2017","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T02:40:39Z","timestamp":1514169639000},"page":"832-840","source":"Crossref","is-referenced-by-count":8,"title":["Mitochondrial dysfunction in iPSC-derived neurons of subjects with chronic mountain sickness"],"prefix":"10.1152","volume":"125","author":[{"given":"Helen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatrics (Respiratory Medicine), University of California San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Perkins","sequence":"additional","affiliation":[{"name":"National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Respiratory Medicine), University of California San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Callacondo","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Health Sciences, Universidad Privada de Tacna, Tacna, Peru"},{"name":"Instituto de Evaluaci\u00f3n de Tecnolog\u00edasen Salud e Investigaci\u00f3n (IETSI). 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