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

Yilin Kang; Alexander J Anderson; Thomas Daniel Jackson; Catherine S Palmer; David P De Souza; Kenji M Fujihara; Tegan Stait; Ann E Frazier; Nicholas J Clemons; Deidreia Tull; David R Thorburn; Malcolm J McConville; Michael T Ryan; David A Stroud; Diana Stojanovski

Journal article

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

Yilin Kang, Alexander J Anderson, Thomas Daniel Jackson, Catherine S Palmer, David P De Souza, Kenji M Fujihara, Tegan Stait, Ann E Frazier, Nicholas J Clemons, Deidreia Tull, David R Thorburn, Malcolm J McConville, Michael T Ryan, David A Stroud, Diana Stojanovski

eLife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2019

DOI: 10.7554/eLife.48828

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

David Thorburn Author Paediatrics Royal Children's Hospital

Malcolm McConville Author Biochemistry and Molecular Biology

Ann Frazier Author Paediatrics Royal Children's Hospital

Catherine Palmer Author Biochemistry and Molecular Biology

Diana Stojanovski Author Biochemistry and Molecular Biology

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Grants

Awarded by Australian Research Council

Awarded by NHMRC

Awarded by Victorian Cancer Agency

Funding Acknowledgements

Australian Research Council DP170101249 Diana StojanovskiMelbourne International Fee Remission Scholarship Yilin KangMelbourne International Research Scholarship Yilin KangMito Foundation Research Fellowship Diana StojanovskiNHMRC David R Thorburn Michael T RyanNHMRC Project Grant 1125390 David R Thorburn Michael T Ryan David A StroudNHMRC Project Grant 1107094 David R Thorburn Michael T Ryan David A StroudNHMRC Project Grant 1140906 Michael T Ryan David A StroudNHMRC Fellowship 1140851 David A StroudNHMRC Fellowship 1022896 David R ThorburnNHMRC Fellowship 1059530 Malcolm J McConvilleVictorian Cancer Agency MCRF16002 Nicholas J ClemonsThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.