Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza St. 63, 80-308, Gdansk, Poland.
Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
Sci Rep. 2023 Jan 14;13(1):766. doi: 10.1038/s41598-023-27914-8.
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.
足细胞构成肾小球滤过屏障的外层，其损伤是肾脏疾病的标志。线粒体功能障碍常伴随着足细胞损伤，并与氧化应激和细胞凋亡的增加有关。β-氨基异丁酸（BAIBA）属于天然β-氨基酸，具有抗炎和抗氧化作用。据报道，BAIBA 参与调节线粒体动力学，但尚不清楚 BAIBA 是否影响足细胞的生物能量学。本研究表明，人足细胞表达 BAIBA 受体，即 MRGPRD，对 BAIBA 刺激敏感。用 L-BAIBA 处理足细胞可显著增加其呼吸参数，如基础呼吸和最大呼吸、三磷酸腺苷（ATP）产生和备用呼吸能力。我们还发现 L-BAIBA 改变了线粒体的数量、大小和形状，促进了细胞器的伸长和分支。L-BAIBA 显著上调过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）和转录因子 A 线粒体（TFAM），表明线粒体生物发生增加。我们的结果表明了足细胞中线粒体动力学的一种新的调节机制，这对于维持其在肾脏滤过屏障中的功能以及促使进一步研究在病理状态下预防或改善足细胞中线粒体损伤可能很重要。
