Table 1.
Phenotypes of cardiac disease models with genetic interventions related to the mitophagy pathways
| Target gene | Gene manipulation | Conditions | Mitophagy | Mitochondrial phenotype | Cardiac phenotype | Refs. |
|---|---|---|---|---|---|---|
| Ubiquitin-dependent mitophagy | ||||||
| Parkin | Germ-line KO | Baseline | – | Normal | Normal | 21 |
| Germ-line KO | MI | – | Dysfunction | Increased injury | 21 | |
| Germ-line KO | Baseline | Preserved | Mild dysfunction | Normal | 79 | |
| Germ-line KO | Sepsis | Preserved | Dysfunction | Normal | 79 | |
| Germ-line KO | DOX | Reduced | Dysfunction | Increased injury | 80 | |
| Germ-line KO | IPC | – | – | Increased injury | 28 | |
| Cardiac-specific inducible KO | Baseline (perinatal) | Reduced | Dysfunction | Lethal cardiomyopathy | 13 | |
| Cardiac-specific inducible KO | Baseline (adult) | – | Normal | Normal | 22 | |
| Cardiac-specific TG | Baseline | Increased | Normal | Normal | 22 | |
| Pink1 | Germ-line KO | Baseline | Reduced | Dysfunction | Dysfunction | 81 |
| Germ-line KO | TAC | Reduced | Dysfunction | Increased injury | 81 | |
| Germ-line KO | Exercise | Reduced | – | – | 82 | |
| Cardiac-specific TG | Baseline | – | – | Normal | 83 | |
| Cardiac-specific TG | I/R | – | – | Reduced injury | 83 | |
| Receptor-dependent mitophagy | ||||||
| Bnip3 | Germ-line KO | Baseline | – | – | Normal | 84 |
| Germ-line KO | I/R | – | – | Reduced injury | 84 | |
| Cardiac-specific inducible TG | Baseline | – | – | Dysfunction | 84 | |
| Cardiac-specific inducible TG | MI | – | – | Increased injury | 84 | |
| Nix | Germ-line KO | Baseline | – | – | Dysfunction | 85 |
| Cardiac-specific KO | Baseline | – | – | Normal | 86 | |
| Cardiac-specific KO | TAC | – | – | Preserved function | 86 | |
| Cardiac-specific TG | Baseline | – | – | Dysfunction | 87 | |
| Fundc1 | Cardiac-specific KO | Baseline | – | Dysfunction | Dysfunction | 88 |
| Cardiac-specific KO | MI | – | Dysfunction | Increased injury | 88 | |
| Fusion/fission-related genes | ||||||
| Mfn1/2 | Cardiac-specific KO | Baseline | – | – | Lethal cardiomyopathy | 89 |
| Cardiac-specific KO | Baseline | – | – | Lethal cardiomyopathy | 90 | |
| Cardiac-specific inducible KO | Baseline | – | Dysfunction | Dysfunction | 90 | |
| Cardiac-specific inducible KO | Baseline | – | Dysfunction | Dysfunction | 91 | |
| Cardiac-specific KO | Baseline | – | – | Lethal cardiomyopathy | 92 | |
| Cardiac-specific inducible KO | Baseline | – | Dysfunction | Dysfunction | 92 | |
| Cardiac-specific inducible KO | I/R | – | – | Reduced injury | 93 | |
| Drp1 | Muscle-specific KO | Baseline | – | Dysfunction | Lethal cardiomyopathy | 94 |
| Cardiac-specific KO (homo) | Baseline | – | Dysfunction | Lethal cardiomyopathy | 24 | |
| Cardiac-specific KO (hetero) | Baseline | – | Dysfunction | Dysfunction | 24 | |
| Cardiac-specific inducible KO | Baseline | Increased | Dysfunction | Dysfunction | 91 | |
| Cardiac-specific inducible KO | Baseline | Reduced | Dysfunction | Dysfunction | 25 | |
| Cardiac-specific KO (hetero) | Baseline | Reduced | Dysfunction | Dysfunction | 25 | |
| Cardiac-specific KO (hetero) | I/R | Reduced | Dysfunction | Increased injury | 25 | |
| Cardiac-specific KO (hetero) | TAC | Reduced | Dysfunction | Increased injury | 30 | |
| Opa1 | Germ-line KO (hetero) | Baseline | – | Dysfunction | Normal | 95 |
| Germ-line KO (hetero) | TAC | – | – | Increased injury | 95 | |
DOX, doxorubicin; I/R, ischaemia/reperfusion; IPC, ischaemic preconditioning; KO, knock-out; MI, myocardial infarction; TAC, transverse aortic constriction; TG, transgenic.