Podocytes constitute an external layer of the glomerular filtration barrier, injury to which is a hallmark of renal disease. Mitochondrial dysfunction often accompanies podocyte damage and is associated with an increase in oxidative stress and apoptosis. β-Aminoisobutyric acid (BAIBA) belongs to natural β-amino acids and is known to exert anti-inflammatory and antioxidant effects. BAIBA has been reported to be involved in regulating mitochondrial dynamics, but unknown is whether BAIBA influences podocyte bioenergetics. The present study showed that human podocytes express the BAIBA receptor, Mas-related G protein-coupled receptor type D (MRGPRD), which is sensitive to BAIBA stimulation. The treatment of podocytes with L-BAIBA significantly increased their respiratory parameters, such as basal and maximal respiration, adenosine triphosphate (ATP) production, and spare respiratory capacity. We also found that L-BAIBA altered mitochondrial quantity, size, and shape, promoting organelle elongation and branching. L-BAIBA significantly upregulated peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) and transcription factor A mitochondrial (TFAM), indicating an increase in mitochondrial biogenesis. Our results demonstrate a novel regulatory mechanism of mitochondrial dynamics in podocytes, which may be important for maintaining their functions in the renal filtration barrier and prompting further investigations of preventing or ameliorating mitochondrial damage in podocytes in pathological states.
Bibliographical noteFunding Information:
This research was supported by a grant from the National Science Center (No. 2016/23/D/NZ5/01449) to I. Audzeyenka and Mossakowski Medical Research Institute, Polish Academy of Sciences.
© 2023, The Author(s).
- Organelle Biogenesis
- Oxidative Stress
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics