Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis

C Liang; S Zhang; D Robinson; MV Ploeg; R Wilson; J Nah; D Taylor; S Beh; R Lim; L Sun; DM Muoio; DA Stroud; L Ho

Journal article

Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis

C Liang, S Zhang, D Robinson, MV Ploeg, R Wilson, J Nah, D Taylor, S Beh, R Lim, L Sun, DM Muoio, DA Stroud, L Ho

Cell Reports | Published : 2022

DOI: 10.1016/j.celrep.2022.111204

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Abstract

Electron transport chain (ETC) biogenesis is tightly coupled to energy levels and availability of ETC subunits. Complex III (CIII), controlling ubiquinol:ubiquinone ratio in ETC, is an attractive node for modulating ETC levels during metabolic stress. Here, we report the discovery of mammalian Co-ordinator of mitochondrial CYTB (COM) complexes that regulate the stepwise CIII biogenesis in response to nutrient and nuclear-encoded ETC subunit availability. The COMA complex, consisting of UQCC1/2 and membrane anchor C16ORF91, facilitates translation of CIII enzymatic core subunit CYTB. Subsequently, microproteins SMIM4 and BRAWNIN together with COMA subunits form the COMB complex to stabilize n..

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University of Melbourne Researchers

David Stroud Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

We thank Shang Li (Duke-NUS) for the kind provision of lentiviral constructs and advice for Crispr/Cas9-mediated knockout generation, Ann-Marie Chacko (Duke-NUS) for the supervision of radioisotope-related work, and Xu Dan (Duke-NUS) for generating the Br mouse knockout. This work was funded by NRF-NRFF2017-05 and HHMI IRSP 55008732 awarded to L.H., and by RECA RECA(Pilot)/2019/0045 awarded to L.H. and D.M. S.Z. is supported by a KTP postdoctoral fellowship. L.S. is supported by OF-IRG, MOH000954, and MOH-000379. D.S. is supported by grants from the Australian National Health and Medical Research Council (NHMRC Project Grant 1140906 and NHMRC Fellowships 1140851). We acknowledge the support of the Mito Foundation (Australia) for the provision of mass spectrometry instrumentation through the large equipment grant support scheme. We thank the Bio21 Mass Spectrometry and Proteomics Facility (MMSPF) for provision of instrumentation, training, and technical support.