Table 2.
Studies of PGC-1α or PGC-1β knockout models
| First author, year (Ref.) | Model | Mito DNA | Mito density (EM) | OXPHOS mRNA/protein | Non-OXPHOS mRNA/protein | Mito energetics | Exercise capacity | Insulin sensitivity | Other |
|---|---|---|---|---|---|---|---|---|---|
| Lin, 2004 (69); Arany, 2005 (68) | PGC-1α whole-body KO | Normal | 30–60% ↓ mRNA; 50% ↓ CytC protein | ATP levels ↓ 20% in heart | 10–50% ↓ cardiac contractile performance | ↑ whole-body | ↓ body weight, increased AMP kinase activity | ||
| Leone, 2005 (67) | PGC-1α whole-body KO | 30% ↓ | 40–60% ↓ mRNA | 10% ↓ in state 3 respiration | 50% ↓ fatigue resistance, abnormal cardiac response to stress | ↑ whole-body | Hepatic steatosis | ||
| Lehman, 2008 (61) | PGC-1α whole-body KO | ↓ cristae density in heart | Slight ↓ mRNA | 60% ↓ in metabolic efficiency | ↓ cardiac power | ||||
| Handschin, 2007 (63,64) | PGC-1α muscle-specific KO | Normal | 30–40% ↓ mRNA | 50% ↓ ALAS1 | 60% ↓ grip strength, endurance, muscle damage basal and exercise | ↑ muscle | ↓ food consumption, ↓ body weight, muscle inflammation, β-cell dysfunction | ||
| Lai, 2008 (62) | PGC-1β whole-body KO | Not changed (heart) | Modest ↓ in state 3 respiration | ↓ running duration | |||||
| Lelliot, 2006 (66) | PGC-1β whole-body KO | ↓ 20% | 20–40% ↓ mRNA | ↓ state 3 and 4 respiration, ↓ ATP synthesis | ↓ chronotropic response to dobutamine | Normal | ↓ body weight, hepatic steatosis on high-fat diet | ||
| Vianna, 2006 (65) | PGC-1β whole-body hypomorph | ↓ 30% | 20–30% ↓ mRNA | Normal | ↑ hepatic lipid levels | ||||
| Sonoda, 2007 (59) | PGC-1β whole-body hypomorph | Normal | 30–40% ↓ mRNA | Normal | Normal | Hepatic steatosis on high-fat diet | |||
| Lai, 2008 (62) | PGC-1α and PGC-1β muscle-specific KO | ↓ 60%, heart | Perinatal lethality due to cardiac failure | Perinatal lethality due to cardiac failure |
↓, Decrease; ↑, increase; KO, knockout; CytC, cytochrome C; ALAS1, 5-aminolevulinate synthase 1.