Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying mohr-tranebjærg syndrome

Y Kang; AJ Anderson; TD Jackson; CS Palmer; DP De Souza; KM Fujihara; T Stait; AE Frazier; NJ Clemons; D Tull; DR Thorburn; MJ McConville; MT Ryan; DA Stroud; D Stojanovski

Journal article

Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying mohr-tranebjærg syndrome

Y Kang, AJ Anderson, TD Jackson, CS Palmer, DP De Souza, KM Fujihara, T Stait, AE Frazier, NJ Clemons, D Tull, DR Thorburn, MJ McConville, MT Ryan, DA Stroud, D Stojanovski

Elife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2019

DOI: 10.7554/eLife.48828

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Abstract

Human Tim8a and Tim8b are members of an intermembrane space chaperone network, known as the small TIM family. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg 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 ch..

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University of Melbourne Researchers

Yilin Kang Author

Catherine Palmer Author

David de Souza Author

Ann Frazier Author

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Grants

Awarded by University of Melbourne

Funding Acknowledgements

[ "Australian Research Council DP170101249 Diana Stojanovski", "Melbourne International Fee Remission Scholarship Yilin Kang", "Melbourne International Research Scholarship Yilin Kang", "Mito Foundation Research Fellowship Diana Stojanovski", "NHMRC David R Thorburn Michael T Ryan", "NHMRC Project Grant 1125390 David R Thorburn Michael T Ryan David A Stroud", "NHMRC Project Grant 1107094 David R Thorburn Michael T Ryan David A Stroud", "NHMRC Project Grant 1140906 Michael T Ryan David A Stroud", "NHMRC Fellowship 1140851 David A Stroud", "NHMRC Fellowship 1022896 David R Thorburn", "NHMRC Fellowship 1059530 Malcolm J McConville", "Victorian Cancer Agency MCRF16002 Nicholas J Clemons", "The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication." ]