| First Author | Abe Y | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 10 | Pages | F1477-90 |
| PubMed ID | 24049142 | Mgi Jnum | J:202951 |
| Mgi Id | MGI:5523407 | Doi | 10.1152/ajprenal.00182.2013 |
| Citation | Abe Y, et al. (2013) TGF-beta1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in cultured mouse podocytes, mediated in part by the mTOR pathway. Am J Physiol Renal Physiol 305(10):F1477-90 |
| abstractText | Transforming growth factor (TGF)-beta has been associated with podocyte injury; we have examined its effect on podocyte bioenergetics. We studied transformed mouse podocytes, exposed to TGF-beta1, using a label-free assay system, Seahorse XF24, which measures oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Both basal OCR and ATP generation-coupled OCR were significantly higher in podocytes exposed to 0.3-10 ng/ml of TGF-beta1 for 24, 48, and 72 h. TGF-beta1 (3 ng/ml) increased oxidative capacity 75%, and 96% relative to control after 48 and 72 h, respectively. ATP content was increased 19% and 30% relative to control after a 48- and 72-h exposure, respectively. Under conditions of maximal mitochondrial function, TGF-beta1 increased palmitate-driven OCR by 49%. Thus, TGF-beta1 increases mitochondrial oxygen consumption and ATP generation in the presence of diverse energy substrates. TGF-beta1 did not increase cell number or mitochondrial DNA copy number but did increase mitochondrial membrane potential (MMP), which could explain the OCR increase. Reactive oxygen species (ROS) increased by 32% after TGF-beta1 exposure for 48 h. TGF-beta activated the mammalian target of rapamycin (mTOR) pathway, and rapamycin reduced the TGF-beta1-stimulated increases in OCR, ECAR, ATP generation, cellular metabolic activity, and protein generation. Our data suggest that TGF-beta1, acting, in part, via mTOR, increases mitochondrial MMP and OCR, resulting in increased ROS generation and that this may contribute to podocyte injury. |
