Journal article
Human Tim8a, Tim8b and Tim13 are auxiliary assembly factors of mature Complex IV
Alexander J Anderson, Jordan J Crameri, Ching-Seng Ang, Tess R Malcolm, Yilin Kang, Megan J Baker, Catherine S Palmer, Alice J Sharpe, Luke E Formosa, Katherine Ganio, Michael J Baker, Christopher A McDevitt, Michael T Ryan, Megan J Maher, Diana Stojanovski
EMBO Reports | Wiley | Published : 2023
Abstract
Human Tim8a and Tim8b are paralogous intermembrane space proteins of the small TIM chaperone family. Yeast small TIMs function in the trafficking of proteins to the outer and inner mitochondrial membranes. This putative import function for hTim8a and hTim8b has been challenged in human models, but their precise molecular function(s) remains undefined. Likewise, the necessity for human cells to encode two Tim8 proteins and whether any potential redundancy exists is unclear. We demonstrate that hTim8a and hTim8b function in the assembly of cytochrome c oxidase (Complex IV). Using affinity enrichment mass spectrometry, we define the interaction network of hTim8a, hTim8b and hTim13, identifying ..
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Grants
Awarded by Australian Research Council (ARC)
Awarded by NHMRC
Awarded by Australian Research Council
Funding Acknowledgements
We acknowledge support from the Mito Foundation to the Stojanovski Lab (Incubator and Booster Grant). AJA, JC and MeJB are supported by Australian Government RTP Scholarships and Mito Foundation top-up scholarships. MJM acknowledges funding by the Australian Research Council (ARC) Future Fellowship (FT180100397), Discovery Project Grant (DP220102030) and NHMRC Project Grant (GNT1165217; to MTR and MJM). LEF acknowledges support from the Mito Foundation and the NHMRC (Investigator Grant 2010149). We thank the University of Melbourne Mass Spectrometry and Proteomics Facility, Biological Optical Microscopy Platform and Flow Cytometry Platform. AUC analyses were carried out by Dr Yee-Foong Mok at Melbourne Protein Characterisation Facility (Bio21). We thank Ms Ellanor Goyne for contributions to protein production; Dr Shadi Maghool for assistance with the Cu(I)-binding assay; A/Prof. David Stroud (University of Melbourne) for discussion and reagents.