Abstract
Proper podocyte function within the glomerulus demands a high and continuous energy supply that is mainly derived from the respiratory chain of the inner mitochondrial membrane. Dysregulations in the metabolic homeostasis of podocytes may result in podocyte damage and glomerular disease. This article highlights the current knowledge about podocyte energy supply by the respiratory chain. We review the regulation of mitochondrial oxidative metabolism with regard to podocytopathy and discuss the latest understanding of different mitochondrial dysfunctions of the podocyte in diabetic nephropathy and focal segmental glomerulosclerosis (FSGS). We discuss genetic forms of mitochondriopathy of the podocyte and end with recent knowledge about crosstalk between NADH and NADPH and potential therapeutic options for podocyte mitochondriopathy. We aim to raise awareness for the complex and interesting mechanisms of podocyte damage by impaired energy supply that, despite of novel findings in recent years, is poorly understood so far.
Highlights
Mitochondria are essential intracellular organelles that play a major role in maintaining the energy homeostasis of cells by synthesis of adenosine triphosphate (ATP) through oxidative phosphorylation
NADH dehydrogenase, cytochrome c reductase, cytochrome c oxidase, and cytochrome c transfer electrons and protons across the inner mitochondrial membrane generating the electrochemical gradient for ATP synthesis in complex V (Figure 1)
Some oxygen molecules are not reduced into water during oxidative phosphorylation but form reactive oxygen species (ROS) that can be converted into highly reactive radicals
Summary
Mitochondria are essential intracellular organelles that play a major role in maintaining the energy homeostasis of cells by synthesis of adenosine triphosphate (ATP) through oxidative phosphorylation. This article highlights the current knowledge of podocyte energy supply by the respiratory chain and the importance of mitochondria for proper podocyte function. In most studies mitochondrial function was characterized using Seahorse Bioscience XF24 Extracellular Flux Analyzer to monitor cell respiration [10,11,12]. With this technique, different metabolic states of cells can be measured in culture and blockers of different complexes of the respiratory chain can be used. As a complex I inhibitor reduced oxygen consumption rate to 25% of the baseline rates, mitochondrial respiration seems to be accounted for 75% of the total cellular respiration in podocytes. Similar to the aforementioned studies, we recently measured podocyte metabolic profiles under diabetic conditions in www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
