title: Mitochondria-targeted therapies for acute kidney injury.
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.
authors.affiliation: IIS-Fundacion Jimenez Diaz,Madrid,Spain.
authors.forename: Luis Carlos
authors.initials: LC
authors.lastname: Tábara
authors.affiliation: IIS-Fundacion Jimenez Diaz,Madrid,Spain.
authors.forename: Jonay
authors.initials: J
authors.lastname: Poveda
authors.affiliation: IIS-Fundacion Jimenez Diaz,Madrid,Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Martin-Cleary
authors.affiliation: REDINREN,Madrid,Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.affiliation: IIS-Fundacion Jimenez Diaz,Madrid,Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: REDINREN,Madrid,Spain.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Sanchez-Niño
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D016572:Cyclosporine