Brinkkoetter, Paul T., Bork, Tillmann, Salou, Sarah, Liang, Wei, Mizi, Athanasia ORCID: 0000-0002-4313-491X, Oezel, 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 ORCID: 0000-0002-5245-1781, Schlimpert, Manuel, Kammerer, Bernd, Handschin, Christoph ORCID: 0000-0003-0603-1097, Schell, Christoph and Huber, Tobias B. ORCID: 0000-0001-7175-5062 (2019). Anaerobic Glycolysis Maintains the Glomerular Filtration Barrier Independent of Mitochondrial Metabolism and Dynamics. Cell Reports, 27 (5). S. 1551 - 1572. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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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-1 alpha, 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).

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brinkkoetter, Paul T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bork, TillmannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salou, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liang, WeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mizi, AthanasiaUNSPECIFIEDorcid.org/0000-0002-4313-491XUNSPECIFIED
Oezel, CemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koehler, SybilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hagmann, H. HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ising, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuczkowski, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schnyder, SveniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abed, AhmedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kretz, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puelles, Victor G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lagies, SimonUNSPECIFIEDorcid.org/0000-0002-5245-1781UNSPECIFIED
Schlimpert, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kammerer, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Handschin, ChristophUNSPECIFIEDorcid.org/0000-0003-0603-1097UNSPECIFIED
Schell, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, Tobias B.UNSPECIFIEDorcid.org/0000-0001-7175-5062UNSPECIFIED
URN: urn:nbn:de:hbz:38-150248
DOI: 10.1016/j.celrep.2019.04.012
Journal or Publication Title: Cell Reports
Volume: 27
Number: 5
Page Range: S. 1551 - 1572
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FOCAL-SEGMENTAL GLOMERULOSCLEROSIS; PODOCYTE ENERGY-METABOLISM; PROTECTS; PROGRESSION; DIFFERENTIATION; ACTIVATION; PATHOLOGY; PATHWAYS; HEALTH; CELLSMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15024

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