Table 2.
Clinical and experimental drugs that that shown efficacy at activating and inhibiting autophagy and mitophagy, including the putative mechanism of active, and mitophagy-specific reference
| Drug | Putative autophagic action | Reference |
|---|---|---|
| Autophagy/mitophagy activators | ||
| AICAR | AMPK-dependent inhibition of mTOR | 61 |
| Betulinic acid | AKT-mTOR inhibitor | 62 |
| BEZ235 | mTOR inhibitor | 63 |
| Carbamazepine | IMPase inhibitor and mTOR-independent activator | 64 |
| 3-Carboxyl proxyl nitroxide | AMPK-dependent inhibition of mTOR | 65 |
| CCI-779 | mTOR inhibitor | 66 |
| Ceramide | (i) AKT-mTOR inhibitor | 67 |
| (ii) Dissociation of the Beclin 1:Bcl-2 complex | ||
| Lithium chloride | IMPase inhibitor and mTOR-independent activator | 68 |
| Metformin | AMPK-dependent inhibition of mTOR | 69 |
| MDL-28170 | Inhibition of calpains I and II and subsequent cleavage of autophagic machinery | 70 |
| Mitochondrial toxins | ROS-induced translocation of Parkin to mitochondria | 71,72 |
| Mito-metformin | AMPK-dependent inhibition of mTOR | 65 |
| Nicotinamide derivatives | SIRT1 activators | 73 |
| Olanzapine | (i) ROS-induction of FoxO transcription factor | 74 |
| (ii) AMPK-dependent inhibition of mTOR | ||
| p62-mediated mitophagy inducer (PMI) | Parkin-dependent and -independent mitophagy | 75 |
| Phenanthroline | Mitochondrial fission | 76 |
| Rapamycin | mTOR inhibitor | 77 |
| RAD001 | mTOR inhibitor | 63 |
| Resveratrol | NAD+-dependent deacetylase and mTOR-independent activator | 78 |
| Rilmenidine | mTOR inhibitor | 79 |
| Selenite | Superoxide-induced mitochondrial damage | 80,81 |
| Spermidine | Acetyltransferase inhibitor and mTOR-independent activator | 82 |
| Trehalose | mTOR-independent activator | 83 |
| Urolithin A | (i) Mitochondrial fission | 84 |
| (ii) AMPK-dependent inhibition of mTOR | ||
| Autophagy/mitophagy inhibitors | ||
| Acid protease inhibitors | Lysosomal alkalizers | 85 |
| Ammonium chloride | Lysosomal alkalizer | 86 |
| Antioxidants (butylated hydroxyanisole, N-acetylcysteine) | (i) Protection of mitochondrial from ROS-mediated damage | 87 |
| (ii) Inhibition of the MPTP | ||
| Bafilomycin A1 | Vacuolar-type H+-ATPase inhibitor | 88 |
| Brefeldin A | Inhibitor of intracellular protein transport and alternative (Atg5/Atg7-independent) autophagy | 89 |
| Chloroquine | Lysosomal alkalizer | 88 |
| Cyclosporine A | Inhibition of the MPTP | 85,87 |
| Idebenone | (i) Protection of mitochondrial from ROS-mediated damage | 90 |
| (ii) Inhibition of the MPTP | ||
| Liensinine diperchlorate | Inhibition of autophagosome–lysosome fusion | 91 |
| LY294002 | Class III PI3K inhibitor | 85 |
| 3-Methyladenine | Class III PI3K inhibitor | 77,85 |
| Mitochondrial division inhibitor 1 (Mdivi-1) | Inhibition of mitochondrial fission | 43 |
| Wortmannin | Nonspecific PI3K inhibitor | 85 |
Abbreviations: AKT, protein kinase B; AMPK, 5′AMP-activated protein kinase; Atg, autophagy-related gene; Bcl-2, B-cell lymphoma 2; IMPase, inositol monophosphatase; MPTP, mitochondrial permeability transition pore; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; ROS, reactive oxygen species; SIRT, sirtuin.