Anaerobic Glycolysis Maintains the Glomerular Filtration Barrier Independent of Mitochondrial Metabolism and Dynamics
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4501447
Author(s) Brinkkoetter, Paul T.; Bork, Tillmann; Salou, Sarah; Liang, Wei; Mizi, Athanasia; Özel, Cem; Koehler, Sybille; Hagmann, H. Henning; Ising, Christina; Kuczkowski, Alexander; Schnyder, Svenia; Abed, Ahmed; Schermer, Bernhard; Benzing, Thomas; Kretz, Oliver; Puelles, Victor G.; Lagies, Simon; Schlimpert, Manuel; Kammerer, Bernd; Handschin, Christoph; Schell, Christoph; Huber, Tobias B.
Author(s) at UniBasel Handschin, Christoph
Year 2019
Title Anaerobic Glycolysis Maintains the Glomerular Filtration Barrier Independent of Mitochondrial Metabolism and Dynamics
Journal Cell Reports
Volume 27
Number 5
Pages / Article-Number 1551-1566.e5
Abstract The cellular responses induced by mitochondrial dysfunction remain elusive. Intrigued by the lack of almost any glomerular phenotype in patients with profound renal ischemia, we comprehensively investigated the primary sources of energy of glomerular podocytes. Combining functional measurements of oxygen consumption rates, glomerular metabolite analysis, and determination of mitochondrial density of podocytes in vivo, we demonstrate that anaerobic glycolysis and fermentation of glucose to lactate represent the key energy source of podocytes. Under physiological conditions, we could detect neither a developmental nor late-onset pathological phenotype in podocytes with impaired mitochondrial biogenesis machinery, defective mitochondrial fusion-fission apparatus, or reduced mtDNA stability and transcription caused by podocyte-specific deletion of Pgc-1α, Drp1, or Tfam, respectively. Anaerobic glycolysis represents the predominant metabolic pathway of podocytes. These findings offer a strategy to therapeutically interfere with the enhanced podocyte metabolism in various progressive kidney diseases, such as diabetic nephropathy or focal segmental glomerulosclerosis (FSGS).
Publisher Elsevier
ISSN/ISBN 2211-1247
edoc-URL https://edoc.unibas.ch/70391/
Full Text on edoc Available
Digital Object Identifier DOI 10.1016/j.celrep.2019.04.012
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/31042480
ISI-Number WOS:000466484100021
Document type (ISI) Journal Article
 
   

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