TGF-beta 1 is a regulator of the pyruvate dehydrogenase complex in fibroblasts
Edward R Smith, Timothy D Hewitson
SCIENTIFIC REPORTS | NATURE RESEARCH | Published : 2020
TGF-β1 reprograms metabolism in renal fibroblasts, inducing a switch from oxidative phosphorylation to aerobic glycolysis. However, molecular events underpinning this are unknown. Here we identify that TGF-β1 downregulates acetyl-CoA biosynthesis via regulation of the pyruvate dehydrogenase complex (PDC). Flow cytometry showed that TGF-β1 reduced the PDC subunit PDH-E1α in fibroblasts derived from injured, but not normal kidneys. An increase in expression of PDH kinase 1 (PDK1), and reduction in the phosphatase PDP1, were commensurate with net phosphorylation and inactivation of PDC. Over-expression of mutant PDH-E1α, resistant to phosphorylation, ameliorated effects of TGF-β1, while inhibit..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) of Australia
The work was supported by a specific project grant from the National Health and Medical Research Council (NHMRC) of Australia (APP1078694).