The Role of Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (PGC-1α) in Kidney Disease

Semin Nephrol. 2018 Mar;38(2):121-126. doi: 10.1016/j.semnephrol.2018.01.003.

Abstract

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a key transcriptional regulator of mitochondrial biogenesis and function. Several recent studies have evaluated the role of PGC-1α in various renal cell types in healthy and disease conditions. Renal tubule cells mostly depend on mitochondrial fatty acid oxidation for energy generation. A decrease in PGC-1α expression and fatty acid oxidation is commonly observed in patient samples and mouse models with acute and chronic kidney disease. Conversely, increasing PGC-1α expression in renal tubule cells restores energy deficit and has been shown to protect from acute and chronic kidney disease. Other kidney cells, such as podocytes and endothelial cells, are less metabolically active and have a narrow PGC-1α tolerance. Increasing PGC-1α levels in podocytes induces podocyte proliferation and collapsing glomerulopathy development, while increasing PGC1-α in endothelial cells alters endothelial function and causes microangiopathy, thus highlighting the cell-type-specific role of PGC-1α in different kidney cells.

Keywords: Notch; PGC-1α; mitochondria; podocyte; tubular cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Kidney Injury / metabolism
  • Animals
  • Endothelial Cells / metabolism
  • Epithelial Cells / metabolism*
  • Fibrosis
  • Gene Expression Regulation
  • Glomerulonephritis / genetics
  • Glomerulonephritis / metabolism
  • Humans
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Tubules / cytology
  • Mitochondria / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Podocytes / metabolism
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / metabolism*

Substances

  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse