Journal article

Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation

G Perez-Siles, A Cutrupi, M Ellis, R Screnci, D Mao, M Uesugi, Eppie M Yiu, Monique M Ryan, BO Choi, G Nicholson, ML Kennerson

SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Charcot-Marie-Tooth (CMT) is a group of inherited diseases clinically and genetically heterogenous, characterised by length dependent degeneration of axons of the peripheral nervous system. A missense mutation (p.R158H) in the pyruvate dehydrogenase kinase 3 gene (PDK3) has been identified as the genetic cause for an X-linked form of CMT (CMTX6) in two unrelated families. PDK3 is one of four PDK isoenzymes that regulate the activity of the pyruvate dehydrogenase complex (PDC). The balance between kinases (PDKs) and phosphatases (PDPs) determines the extend of oxidative decarboxylation of pyruvate to generate acetyl CoA, critically linking glycolysis and the energy producing Krebs cycle. We h..

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Grants

Awarded by National Health and Medical Research Council


Awarded by USA Muscular Dystrophy Association


Funding Acknowledgements

The authors thank the families. This research was supported by the National Health and Medical Research Council Project Grant (APP1007705) awarded to M.L.K. and G.A.N., USA Muscular Dystrophy Association Project Grant (MDA217729) awarded to G.A.N. and M.L.K. and the Professor Tony Basten Fellowship (The University of Sydney) awarded to G.P.S. Dr. Mario A. Saporta and Dr. Renata Maciel for their guidance and advice on iPSC and differentiation protocols.