Key Points
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Healthy mitochondria are essential for normal kidney function; mitochondrial cytopathies can result in renal disease and mitochondrial damage has a role in the pathophysiology of acute kidney injury (AKI)
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Although mitochondrial diseases are characterized by maternal inheritance, many mitochondrial disorders are caused by mutations in nuclear genes and are inherited according to classic Mendelian rules
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Most mitochondrial diseases with kidney involvement cause tubular defects; however, mutations in the coenzyme Q10 biosynthesis pathway and the mtDNA 3243 A>G mutation primarily cause glomerular disease
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Diagnosis of genetic mitochondrial disorders increasingly relies on new sequencing techniques, but thorough biochemical and clinical characterization of patients is essential to guide these analyses
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In AKI, mitochondrial dysfunction precedes and participates in the physiopathology of tissue damage; mitochondrial biogenesis might represent a crucial step in the recovery phase
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Potential therapies that target mitochondrial dynamics, mitophagy and/or mitochondrial biogenesis might limit renal damage during AKI and promote recovery of kidney function
Abstract
Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue.
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Acknowledgements
Mitochondrial studies in S.M.P.'s laboratory are supported by R01-DK0950972. Studies in L.S.'s laboratory are supported by Telethon grants 14187 and 13222.
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Emma, F., Montini, G., Parikh, S. et al. Mitochondrial dysfunction in inherited renal disease and acute kidney injury. Nat Rev Nephrol 12, 267–280 (2016). https://doi.org/10.1038/nrneph.2015.214
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DOI: https://doi.org/10.1038/nrneph.2015.214
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