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Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebj\u00e6rg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells or how mutation of this protein leads to a neurodegenerative disease. We show that hTim8a is required for the assembly of Complex IV in neurons, which is mediated through a transient interaction with Complex IV assembly factors, in particular the copper chaperone COX17. Complex IV assembly defects resulting from loss of hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c, which primes cells for death. Alleviation of oxidative stress with Vitamin E treatment rescues cells from apoptotic vulnerability. We hypothesise that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.<\/jats:p>","DOI":"10.7554\/elife.48828","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T08:00:35Z","timestamp":1572854435000},"source":"Crossref","is-referenced-by-count":56,"title":["Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebj\u00e6rg syndrome"],"prefix":"10.7554","volume":"8","author":[{"given":"Yilin","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia"},{"name":"The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular 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