In Vitro Hypoxia/Reoxygenation Induces Mitochondrial Cardiolipin Remodeling in Human Kidney Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Cardiolipins*/metabolism ; Mitochondria*/metabolism ; Cell Hypoxia* ; Reactive Oxygen Species*/metabolism ; Oxygen*/metabolism; Humans ; Kidney Tubules, Proximal/metabolism ; Kidney Tubules, Proximal/pathology ; Kidney Tubules, Proximal/cytology ; Oxidative Phosphorylation ; Kidney/metabolism ; Kidney/pathology ; Cell Line ; Transferases (Other Substituted Phosphate Groups)/metabolism ; Transferases (Other Substituted Phosphate Groups)/genetics ; Membrane Proteins

Renal ischemia/reperfusion is a serious condition that not only causes acute kidney injury, a severe clinical syndrome with high mortality, but is also an inevitable part of kidney transplantation or other kidney surgeries. Alterations of oxygen levels during ischemia/reperfusion, namely hypoxia/reoxygenation, disrupt mitochondrial metabolism and induce structural changes that lead to cell death. A signature mitochondrial phospholipid, cardiolipin, with many vital roles in mitochondrial homeostasis, is one of the key players in hypoxia/reoxygenation-induced mitochondrial damage. In this study, we analyze the effect of hypoxia/reoxygenation on human renal proximal tubule epithelial cell (RPTEC) cardiolipins, as well as their metabolism and mitochondrial functions. RPTEC cells were placed in a hypoxic chamber with a 2% oxygen atmosphere for 24 h to induce hypoxia; then, they were replaced back into regular growth conditions for 24 h of reoxygenation. Surprisingly, after 24 h, hypoxia cardiolipin levels substantially increased and remained higher than control levels after 24 h of reoxygenation. This was explained by significantly elevated levels of cardiolipin synthase and lysocardiolipin acyltransferase 1 (LCLAT1) gene expression and protein levels. Meanwhile, hypoxia/reoxygenation decreased ADP-dependent mitochondrial respiration rates and oxidative phosphorylation capacity and increased reactive oxygen species generation. Our findings suggest that hypoxia/reoxygenation induces cardiolipin remodeling in response to reduced mitochondrial oxidative phosphorylation in a way that protects mitochondrial function.

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Science Fund of Lithuanian University of Health Sciences Lietuvos Sveikatos Mokslų Universitetas

Keywords: AKI; cardiolipin; hypoxia/reoxygenation; ischemia/reperfusion; kidneys; mitochondria

0 (Cardiolipins)
0 (Reactive Oxygen Species)
S88TT14065 (Oxygen)
EC 2.7.8.- (cardiolipin synthetase)
EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups))
0 (Membrane Proteins)

Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240718

20240718

PMC11172718

10.3390/ijms25116223

38892409