Table 1.
The therapeutic compounds that target mitochondrial dysfunction.
| Therapeutics | Mechanism(s) of Action | Experimental Model | Clinical Trial | References |
|---|---|---|---|---|
| Cardiolipin protection | ||||
| SS-31 | Binds to cardiolipin, prevents peroxidase activity and improves mitochondrial respiration and ATP production; Inhibits cytochrome c release; Normalizes mitochondrial potential (ΔΨm) |
IRI-AKI, UUO, and DKD | Mitochondrial myopathy (NCT02367014) Age-related skeletal muscle mitochondrial dysfunction (NCT02245620) |
[80,96,97,98] |
| SS-20 | Reduces mitochondrial matrix swelling and preserves cristae membranes; Increases ATP and reduces ROS |
IRI-AKI | [99] | |
| Fission inhibitor | ||||
| Mdivi-1 | Selectively inhibits Drp1; Induces mitochondria fusion and increases ATP production |
IRI-AKI, ADPKD, and UUO | [100,101,102] | |
| Biogenesis activator | ||||
| SRT1720 | Sirt-1 activator; Restores renal expression of PGC-1α, mitochondrial mass, ATP levels |
IRI-AKI and UUO | [103,104] | |
| Resveratrol | Sirt-1 activator; Restores mitochondrial respiratory capacity and decreases the production of mtROS and lipid peroxidation |
Hemorrhagic shock induces AKI and db/db mice |
[20,71,105,106,107] | |
| AICAR | AMPK activator; Attenuates nitrosative stress and monocyte/macrophage infiltration |
IRI-AKI and UUO | [13,108,109] | |
| Formoterol | Agonist of β2-adrenoreceptor, increase PGC-1α synthesis and induces mitochondrial biogenesis by increasing mtDNA copy numbers, oxygen consumption rate | IRI-AKI and db/db mice | [110,111,112] | |
| Fenofibrate/Bezafibrate | Peroxisomal proliferator-activated receptor (PPAR)-α agonist, lipid lowering, increases mitochondrial biogenesis | CKD and DKD | Diabetic complications (CVD and DKD) (FIELD, ISRCTN 64783481) |
[113] |
| mPTP inhibitor | ||||
| CSA | Interacts with cyclophilin D; Suppresses mPTP opening and mitochondria swelling |
IRI-AKI | Acute myocardial infarction (NCT01595958) Severe traumatic brain injury (NCT01825044) | [114] |
| TDZD-8 | Selectively inhibits GSK-3β; Diminishes MPT |
Drug-induced AKI and IRI-AKI | [115,116,117] | |
| Antioxidants | ||||
| CoQ10 | Normalizes ATP production, attenuates mtROS and decreases mitochondrial ΔΨm | db/db mice | Mitochondrial disorders (NCT00432744) Parkinson disease (NCT00740714) | [118] |
| MitoQ | ROS scavenger; Antioxidant concentrates at matrix in a ΔΨm-dependent manner |
IRI-AKI Ins2(+/)⁻(AkitaJ) mice |
Parkinson’s disease (NCT00329056) Fatty acid disease (NCT01167088) Hepatitis C (NCT00433108) CKD (NCT02364648) |
[66,119] |
| SkQR1 | Antioxidant and decreased mitochondrial ΔΨm | IRI-AKI and gentamycin-induced renal failure |
[120,121]. | |
| Curcumin | Antioxidant; Alteration of mitochondrial dynamics and bioenergetics. |
5/6NX mice and db/db mice |
Leber hereditary optic neuropathy (NCT00528151) | [122,123,124] |
ATP: adenosine triphosphate; ΔΨm: mitochondrial membrane potential; IRI-AKI: ischemic reperfusion induced acute kidney injury; UUO: unilateral ureter obstruction; DKD: diabetic kidney diseases; ROS: reactive oxygen species; Mdivi-1: Mitochondrial division inhibitor-1; ADPKD: autosomal dominant polycystic kidney disease; Drp1: dynamin related protein 1; Sirt1: Sirtuin 1; PGC-1α: PPARgamma-coactivator-1α; AMPK: AMP-activated protein kinase; mtROS: mitochondria reactive oxidative species; mtDNA: mitochondria DNA; CKD: chronic kidney disease; mPTP: mitochondrial permeability transition pore; CSA: Cyclosporine-A; TDZD-8: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; GSK-3β:, glycogen synthase kinase 3β; CoQ10: Coenzyme Q10 MitoQ: mitochondrial coenzyme Q; SkQR1: 10-(6′-plastoquinonyl) decylrhodamine 19; 5/6NX: five-sixth nephrectomy.