Loss of mitochondrial fatty acid β-oxidation protein short-chain Enoyl-CoA hydratase disrupts oxidative phosphorylation protein complex stability and function

H Burgin; AJ Sharpe; S Nie; M Ziemann; JJ Crameri; D Stojanovski; J Pitt; A Ohtake; K Murayama; M McKenzie

Journal article

Loss of mitochondrial fatty acid β-oxidation protein short-chain Enoyl-CoA hydratase disrupts oxidative phosphorylation protein complex stability and function

H Burgin, AJ Sharpe, S Nie, M Ziemann, JJ Crameri, D Stojanovski, J Pitt, A Ohtake, K Murayama, M McKenzie

FEBS Journal | Published : 2023

DOI: 10.1111/febs.16595

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Abstract

Short-chain enoyl-CoA hydratase 1 (ECHS1) is involved in the second step of mitochondrial fatty acid β-oxidation (FAO), catalysing the hydration of short-chain enoyl-CoA esters to short-chain 3-hyroxyl-CoA esters. Genetic deficiency in ECHS1 (ECHS1D) is associated with a specific subset of Leigh Syndrome, a disease typically caused by defects in oxidative phosphorylation (OXPHOS). Here, we examined the molecular pathogenesis of ECHS1D using a CRISPR/Cas9 edited human cell ‘knockout’ model and fibroblasts from ECHS1D patients. Transcriptome analysis of ECHS1 ‘knockout’ cells showed reductions in key mitochondrial pathways, including the tricarboxylic acid cycle, receptor-mediated mitophagy an..

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University of Melbourne Researchers

Diana Stojanovski Author

Grants

Awarded by Japan Agency for Medical Research and Development

Funding Acknowledgements

This work was supported in part by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED (JP20ek0109468, JP20ek0109482, JP20bm0804018, JP21ek0109511), Deakin University (HJB and MM), the Australian Government, Department of Education Research Training Program Scholarship (HB) and the Australian Mito Foundation (HB). The authors wish to acknowledge the use of the services and facilities of Australian Genome Research Facility (AGRF) and the Mass Spectrometry facility at Bio21, University of Melbourne. Open access publishing facilitated by Deakin University, as part of the Wiley -Deakin University agreement via the Council of Australian University Librarians. Open access publishing facilitated by Deakin University, as part of the Wiley -Deakin University agreement via the Council of Australian University Librarians.