Mitochondria-targeted therapies for acute kidney injury

Luis Carlos Tábara; Jonay Poveda; Catalina Martin-Cleary; Rafael Selgas; Alberto Ortiz; Maria D. Sanchez-Niño

doi:10.1017/erm.2014.14

Mitochondria-targeted therapies for acute kidney injury

Published online by Cambridge University Press: 08 August 2014

Luis Carlos Tábara ,

Jonay Poveda ,

Catalina Martin-Cleary ,

Rafael Selgas ,

Alberto Ortiz and

Maria D. Sanchez-Niño

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Luis Carlos Tábara: Affiliation:
IIS-Fundacion Jimenez Diaz, Madrid, Spain REDINREN, Madrid, Spain
Jonay Poveda: Affiliation:
IIS-Fundacion Jimenez Diaz, Madrid, Spain REDINREN, Madrid, Spain
Catalina Martin-Cleary: Affiliation:
IIS-Fundacion Jimenez Diaz, Madrid, Spain REDINREN, Madrid, Spain
Rafael Selgas: Affiliation:
REDINREN, Madrid, Spain IDIPAZ, Madrid, Spain
Alberto Ortiz: Affiliation:
IIS-Fundacion Jimenez Diaz, Madrid, Spain REDINREN, Madrid, Spain Universidad Autonoma de Madrid, Madrid, Spain IRSIN, Paseo de la Castellana, 260, 28046 Madrid, Spain
Maria D. Sanchez-Niño*: Affiliation:
REDINREN, Madrid, Spain IDIPAZ, Madrid, Spain
*: *Corresponding author: Maria D. Sanchez-Niño, Paseo de la Castellana, 260, 28046 Madrid, Spain. E-mail: [email protected]

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Abstract

Acute kidney injury (AKI) is a serious clinical condition with no effective treatment. Tubular cells are key targets in AKI. Tubular cells and, specifically, proximal tubular cells are extremely rich in mitochondria and mitochondrial changes had long been known to be a feature of AKI. However, only recent advances in understanding the molecules involved in mitochondria biogenesis and dynamics and the availability of mitochondria-targeted drugs has allowed the exploration of the specific role of mitochondria in AKI. We now review the morphological and functional mitochondrial changes during AKI, as well as changes in the expression of mitochondrial genes and proteins. Finally, we summarise the current status of novel therapeutic strategies specifically targeting mitochondria such as mitochondrial permeability transition pore (MPTP) opening inhibitors (cyclosporine A (CsA)), quinone analogues (MitoQ, SkQ1 and SkQR1), superoxide dismutase (SOD) mimetics (Mito-CP), Szeto-Schiller (SS) peptides (Bendavia) and mitochondrial division inhibitors (mdivi-1). MitoQ, SkQ1, SkQR1, Mito-CP, Bendavia and mdivi-1 have improved the course of diverse experimental models of AKI. Evidence for a beneficial effect of CsA on human cardiac ischaemia–reperfusion injury derives from a clinical trial; however, CsA is nephrotoxic. MitoQ and Bendavia have been shown to be safe for humans. Ongoing clinical trials are testing the efficacy of Bendavia in AKI prevention following renal artery percutaneous transluminal angioplasty.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 16 , 2014 , e13

DOI: https://doi.org/10.1017/erm.2014.14 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2014

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Mitochondria-targeted therapies for acute kidney injury

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Mitochondria-targeted therapies for acute kidney injury

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