Mahtab Tavasoli, Sarah Lahire, Stanislav Sokolenko, Robyn Novorolsky, Sarah Anne Reid, Abir Lefsay, Meredith O C Otley, Kitipong Uaesoontrachoon, Joyce Rowsell, Sadish Srinivassane, Molly Praest, Alexandra MacKinnon, Melissa Stella Mammoliti, Ashley Alyssa Maloney, Marina Moraca, J Pedro Fernandez-Murray, Meagan McKenna, Christopher J Sinal, Kanneboyina Nagaraju, George S Robertson, Eric P Hoffman, Christopher R McMaster
CHKB encodes one of two mammalian choline kinase enzymes that catalyze the first step in the synthesis of the membrane phospholipid phosphatidylcholine. In humans and mice, inactivation of the CHKB gene (Chkb in mice) causes a recessive rostral-to-caudal muscular dystrophy. Using Chkb knockout mice, we reveal that at no stage of the disease is phosphatidylcholine level significantly altered. We observe that in affected muscle a temporal change in lipid metabolism occurs with an initial inability to utilize fatty acids for energy via mitochondrial β-oxidation resulting in shunting of fatty acids into triacyglycerol as the disease progresses...
March 23, 2022: Nature Communications