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Prominent Mitochondrial Injury as an Early Event in Heme Protein-Induced Acute Kidney Injury
Raman Deep Singh1, Anthony J Croatt1, Allan W Ackerman1
1Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic Rochester, Minnesota.
Kidney360
|December 14, 2022
Summary
Heme protein-induced acute kidney injury (AKI) impairs mitochondrial function, leading to reduced ATP and NAD+ levels. This study reveals mitochondrial structural damage and suggests NAD+ boosting agents as potential therapies for this form of AKI.
Area of Science:
- Nephrology
- Mitochondrial Biology
- Cellular Injury
Background:
- Mitochondrial injury is a key factor in acute kidney injury (AKI).
- Heme protein-induced AKI (HP-AKI) is a significant cause of renal injury.
- Comprehensive analysis of mitochondrial dysfunction in HP-AKI is lacking.
Purpose of the Study:
- To investigate mitochondrial function, quality control, and ultrastructure in HP-AKI.
- To examine the effects of heme exposure on renal proximal tubule epithelial cells.
- To identify potential therapeutic targets for HP-AKI.
Main Methods:
- Utilized a murine glycerol model of HP-AKI, examining samples at 8 and 24 hours.
- Assessed mitochondrial function markers, including ATP and NAD+ levels.
- Analyzed protein expression related to mitochondrial dynamics and quality control.
- Examined mitochondrial ultrastructure using advanced imaging techniques.
- Investigated heme's effects on renal proximal tubule epithelial cells in vitro.
Main Results:
- HP-AKI led to reduced ATP and NAD+ content and altered NAD+/NADH ratio.
- Mitochondrial biogenesis and fusion proteins were downregulated, while fission proteins were upregulated.
- Significant mitochondrial structural abnormalities, including fragmentation and cristae damage, were observed.
- Heme exposure in vitro mimicked the suppression of mitochondrial biogenesis and upregulation of fission.
Conclusions:
- Modern AKI concepts are applicable to HP-AKI.
- Mitochondrial dysfunction is a central mechanism in HP-AKI.
- NAD+-boosting agents and mitoprotective therapies warrant further investigation for HP-AKI treatment.
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