title: Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes.
abstract: Differentiated podocytes, a type of renal glomerular cells, require substantial levels of energy to maintain glomerular physiology. Mitochondria and glycolysis are two major producers of ATP, but the precise roles of each in podocytes remain unknown. This study evaluated the roles of mitochondria and glycolysis in differentiated and differentiating podocytes. Mitochondria in differentiated podocytes are located in the central part of cell body while blocking mitochondria had minor effects on cell shape and migratory ability. In contrast, blocking glycolysis significantly reduced the formation of lamellipodia, a cortical area of these cells, decreased the cell migratory ability and induced the apoptosis. Consistently, the local ATP production in lamellipodia was predominantly regulated by glycolysis. In turn, synaptopodin expression was ameliorated by blocking either mitochondrial respiration or glycolysis. Similar to differentiated podocytes, the differentiating podocytes utilized the glycolysis for regulating apoptosis and lamellipodia formation while synaptopodin expression was likely involved in both mitochondrial OXPHOS and glycolysis. Finally, adult mouse podocytes have most of mitochondria predominantly in the center of the cytosol whereas phosphofructokinase, a rate limiting enzyme for glycolysis, was expressed in foot processes. These data suggest that mitochondria and glycolysis play parallel but distinct roles in differentiated and differentiating podocytes.
authors.affiliation: TMK project, Medical Innovation Center, Kyoto University, Kyoto, Japan.|Pharmacology Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, Saitama, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Ozawa
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Shuko
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Laboratory of Functional Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamura
authors.affiliation: TMK project, Medical Innovation Center, Kyoto University, Kyoto, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mori
authors.affiliation: TMK project, Medical Innovation Center, Kyoto University, Kyoto, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.affiliation: TMK project, Medical Innovation Center, Kyoto University, Kyoto, Japan.|Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Yanagita
authors.affiliation: TMK project, Medical Innovation Center, Kyoto University, Kyoto, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D010085:Oxidative Phosphorylation / Q000187:drug effects; D025221:Phosphofructokinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050199:Podocytes / Q000166:cytology / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C503968:Synpo protein, mouse; C032456:antimycin; D000968:Antimycin A; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D052250:Nitric Oxide Synthase Type III; D025221:Phosphofructokinases