LINC00116-encoded microprotein mitoregulin regulates fatty acid metabolism at the mitochondrial outer membrane

S Zhang; Y Guo; G Fidelito; DRL Robinson; C Liang; R Lim; Z Bichler; R Guo; G Wu; H Xu; QD Zhou; BK Singh; P Yen; D Kappei; DA Stroud; L Ho

Journal article

LINC00116-encoded microprotein mitoregulin regulates fatty acid metabolism at the mitochondrial outer membrane

S Zhang, Y Guo, G Fidelito, DRL Robinson, C Liang, R Lim, Z Bichler, R Guo, G Wu, H Xu, QD Zhou, BK Singh, P Yen, D Kappei, DA Stroud, L Ho

Iscience | Published : 2023

DOI: 10.1016/j.isci.2023.107558

Abstract

LINC00116 encodes a microprotein first identified as Mitoregulin (MTLN), where it was reported to localize to the inner membrane of mitochondria to regulate fatty acid oxidation and oxidative phosphorylation. These initial discoveries were followed by reports with differing findings about its molecular functions and submitochondrial localization. To clarify the apparent discrepancies, we constructed multiple orthogonal methods of determining the localization of MTLN, including split GFP-based reporters that enable efficient and reliable topology analyses for microproteins. These methods unequivocally demonstrate MTLN primarily localizes to the outer membrane of mitochondria, where it interac..

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University of Melbourne Researchers

Gio Fidelito Author

David Stroud Author

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Grants

Awarded by Duke-NUS Medical School

Funding Acknowledgements

This work was funded by NRF-NRFF2017-05, HHMI IRSP 55008732 awarded to L.H. S.Z. was supported by a KTP postdoctoral fellowship from Duke-NUS Medical School and is supported by start-up funds from the Zhejiang University. D.S. is supported by grants from the Australian National Health and Medical Research Council ( NHMRC Project Grant 1140906 and NHMRC Fellowships 1140851). Q. Z. is supported by the National Natural Science Foundation of China (32171275). 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. We thank Zhaoxiaonan Lin from the Core Facilities, Zhejiang University School of Medicine for their technical support. We thank Zhiwei Ge and Ya'er Zhu (Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University) for their assistance of GC-MS/MS data collection. D.K. is supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative.