Lactate regulates respiratory efficiency and mitochondrial dynamics in primary rat podocytes

• Published in: Free radical biology & medicine 2024-08, Vol.220, p.312-323
• Main Authors: Audzeyenka, Irena, Szrejder, Maria, Rachubik, Patrycja, Grochowalska, Klaudia, Kulesza, Tomasz, Rogacka, Dorota, Narajczyk, Magdalena, Piwkowska, Agnieszka
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Energy Metabolism; Glucose - metabolism; Isoenzymes; L-Lactate Dehydrogenase - metabolism; Lactate dehydrogenase; Lactate Dehydrogenase 5 - metabolism; Lactic Acid - metabolism; LDHA; LDHB; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial biogenesis; Mitochondrial Dynamics; Oxidative phosphorylation; Oxidative Phosphorylation - drug effects; Oxygen Consumption; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Podocytes - metabolism; Podocytes - pathology; Pyruvic Acid - metabolism; Rats
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2024.05.022

Podocytes are crucial for regulating glomerular permeability. They have foot processes that are integral to the renal filtration barrier. Understanding their energy metabolism could shed light on the pathogenesis of filtration barrier injury. Lactate has been increasingly recognized as more than a waste product and has emerged as a significant metabolic fuel and reserve. The recent identification of lactate transporters in podocytes, the expression of which is modulated by glucose levels and lactate, highlights lactate's relevance. The present study investigated the impact of lactate on podocyte respiratory efficiency and mitochondrial dynamics. We confirmed lactate oxidation in podocytes, suggesting its role in cellular energy production. Under conditions of glucose deprivation or lactate supplementation, a significant shift was seen toward oxidative phosphorylation, reflected by an increase in the oxygen consumption rate/extracellular acidification rate ratio. Notably, lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB) isoforms, which are involved in lactate conversion to pyruvate, were detected in podocytes for the first time. The presence of lactate led to higher intracellular pyruvate levels, greater LDH activity, and higher LDHB expression. Furthermore, lactate exposure increased mitochondrial DNA-to-nuclear DNA ratios and resulted in upregulation of the mitochondrial biogenesis markers peroxisome proliferator-activated receptor coactivator-1α and transcription factor A mitochondrial, regardless of glucose availability. Changes in mitochondrial size and shape were observed in lactate-exposed podocytes. These findings suggest that lactate is a pivotal energy source for podocytes, especially during energy fluctuations. Understanding lactate's role in podocyte metabolism could offer insights into renal function and pathologies that involve podocyte injury. [Display omitted] •Lactate serves as an important precursor for cellular energy production in podocytes.•Lactate stimulation alters mitochondrial dynamics and respiratory efficiency.•Lactate augments mitochondrial biogenesis in podocytes.•Lactate regulates LDH isoforms expression and activity in podocytes.