Hyperglycemia alters mitochondrial respiration efficiency and mitophagy in human podocytes
- Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Wita Stwosza St. 63, 80-308, Gdansk (Poland)
- Bristol Renal, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY (United Kingdom)
Highlights: • Impairment of mitochondrial dynamics underlies the pathogenesis of type 2 diabetes. • Mitochondrial respiration is altered in glomeruli isolated from diabetic STZ-rats. • High glucose induces mitochondrial fission and fragmentation in human podocytes. • Mitochondrial fusion, biogenesis and mitophagy are reduced in HG-treated podocytes. • HG can injure the kidney by alteration of podocytes and glomerular bioenergetics. Podocytes constitute the outer layer of the renal glomerular filtration barrier. Their energy requirements strongly depend on efficient oxidative respiration, which is tightly connected with mitochondrial dynamics. We hypothesized that hyperglycemia modulates energy metabolism in glomeruli and podocytes and contributes to the development of diabetic kidney disease. We found that oxygen consumption rates were severely reduced in glomeruli from diabetic rats and in human podocytes that were cultured in high glucose concentration (30 mM; HG). In these models, all of the mitochondrial respiratory parameters, including basal and maximal respiration, ATP production, and spare respiratory capacity, were significantly decreased. Podocytes that were treated with HG showed a fragmented mitochondrial network, together with a decrease in expression of the mitochondrial fusion markers MFN1, MFN2, and OPA1, and an increase in the activity of the fission marker DRP1. We showed that markers of mitochondrial biogenesis, such as PGC-1α and TFAM, decreased in HG-treated podocytes. Moreover, PINK1/parkin-dependent mitophagy was inhibited in these cells. These results provide evidence that hyperglycemia impairs mitochondrial dynamics and turnover, which may underlie the remarkable deterioration of mitochondrial respiration parameters in glomeruli and podocytes.
- OSTI ID:
- 23195508
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 407; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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