Hyperglycemia alters mitochondrial respiration efficiency and mitophagy in human podocytes

Irena Audzeyenka, Patrycja Rachubik, Marlena Typiak, Tomasz Kulesza, Anna Topolewska, Dorota Rogacka, Stefan Angielski, Moin A Saleem, Agnieszka Piwkowska

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

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.

Original languageEnglish
Article number112758
Pages (from-to)112758
JournalExperimental Cell Research
Volume407
Issue number1
Early online date23 Aug 2021
DOIs
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
This research was supported by a grant from the National Science Center (no. 2016/23/D/NZ5/01449 ) to I. Audzeyenka.

Publisher Copyright:
© 2021 The Author(s)

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