Crosstalk Between Lipids and Mitochondria in Diabetic Kidney Disease
Purpose of Review
The goal of this review is to review the role that renal parenchymal lipid accumulation plays in contributing to diabetic kidney disease (DKD), specifically contributing to the mitochondrial dysfunction observed in glomerular renal cells in the context of DKD development and progression.
Mitochondrial dysfunction has been observed in experimental and clinical DKD. Recently, Ayanga et al. demonstrate that podocyte-specific deletion of a protein involved in mitochondrial dynamics protects from DKD progression. Furthermore, our group has recently shown that ATP-binding cassette A1 (a protein involved in cholesterol and phospholipid efflux) is significantly reduced in clinical and experimental DKD and that genetic or pharmacological induction of ABCA1 is sufficient to protect from DKD. ABCA1 deficiency in podocytes leads to mitochondrial dysfunction observed with alterations of mitochondrial lipids, in particular, cardiolipin (a mitochondrial-specific phospholipid). However, through pharmacological reduction of cardiolipin peroxidation DKD progression is reverted.
Lipid metabolism is significantly altered in the diabetic kidney and renders cellular components, such as the podocyte, susceptible to injury leading to worsened DKD progression. Dysfunction of the lipid metabolism pathway can also lead to mitochondrial dysfunction and mitochondrial lipid alteration. Future research aimed at targeting mitochondrial lipids content and function could prove to be beneficial for the treatment of DKD.
KeywordsDiabetic kidney disease Podocyte Mitochondria Cardiolipin ABCA1 Lipid metabolism
GMD and AM prepared a draft of the manuscript. AM focused primarily on the “Lipids in DKD” section and GMD focused primarily on the “Mitochondrial Defects and Dysfunction in DKD” section. AF reviewed and improved the entire manuscript.
Research in Dr. Alessia Fornoni’s laboratory is supported by the NIH grants R01DK117599, R01DK104753, R01CA227493, U54DK083912, UM1DK100846, U01DK116101, and UL1TR000460 (Miami Clinical Translational Science Institute).
Compliance with Ethical Standards
Conflict of Interest
Alessia Fornoni is an investor on pending or issued patents (US 10,183,038 and US 10,052,345) aimed at diagnosing or treating proteinuric kidney diseases. She stands to gain royalties from the future commercialization of these patents. She is Chief Scientific Officer of L&F Health LLC and is a consultant for Variant Pharmaceuticals. Variant Pharmaceuticals has licensed worldwide rights from L&F Research to develop and commercialize hydroxypropyl-beta-cyclodextrin for the treatment of kidney disease. She is the founder of LipoNexT LLC. She is also supported by Roche and Boehringer Ingelheim.
Michelle Ducasa and Alla Mitrofanova declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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