Table 1.
In vivo evidence of ATF4 activation by mitochondrial stress
| Tissue | Evidence | Ref | Others | |
|---|---|---|---|---|
| Transgenic mice systemically expressing dominant patient mutation of mitochondrial DNA helicase (deletor mice) | Muscle | Mthfd2 and Fgf21 gene induction | (29) | Associates with AKT activation |
| Cox10 deficient mice | Muscle | Mthfd2 and Fgf21 gene induction | (29) | Associates with AKT activation |
| Metformin treatment | Liver | Increased ATF4 protein and Fgf21 gene induction | (30) | |
| Skeletal muscle-specific UCP1 overexpression | Skeletal muscle | Increased ATF4 protein and Fgf21 gene induction | (32) | |
| Systemic expression of dominant negative ALDH2 | Heart | Increased ATF4 target gene induction | (36) | Heterozygous deletion of ATF4 diminished the response |
| Frataxin knockout | Muscle | Increased ATF4 target gene induction | (37) | |
| Skeletal muscle-specific ATG7 knockout | Skeletal muscle | Increased Fgf21 gene induction in skeletal muscle | (38) | |
| Skeletal muscle-specific Mfn1 and Mfn2 double knockout | Skeletal muscle | Increased ATF4 protein and eIF2α phosphorylation in skeletal muscle | (38) |