Table 2.
Amino acids associated metabolites regulating mitophagy
| Metabolite | Molecular Formula | Metabolic Precursor | Effect on Mitophagy |
|---|---|---|---|
| Ammonia | NH4+ | Amino acid (oxidative deamination) | Ammonia promotes the expression of BNIP3, PINK1 and PRKN, thus facilitates mitophagy. |
| Glutamate | C5H9NO4 | Glutamine (glutaminolysis) | Glutamate induces Ca2+ entry leading to RHOT1-dependent PRKN translocation and mitophagy. |
| GABA | C₄H₉NO₂ | Glutamate | GABA activates MTOR and inhibits mitophagy. |
| NO | NO | Arginine (catalyzed by NOS) | NO triggers S-nitrosylation of PRKN and PRKN translocation to initiate mitophagy. S-nitrosylation of PINK1 and PRKN impairs mitophagy. NO disturbs phagophore formation to suppress mitophagy. |
| Spermidine | C7H19N3 | Arginine | Spermidine activates ATM kinase-dependent activation of PINK1-PRKN pathway. Spermidine induces the expression of BECN1, MAP1LC3, PINK1, PRKN, ULK1, ATGs, AMPK activation and MTOR inhibition. |
| Melatonin | C13H16N2O2 | Tryptophan | Melatonin suppresses ROS-mediated EIF2AK4-ATF4-BNIP3 axis-dependent mitophagy. Melatonin antagonizes mitophagy via PPARG-FUNDC1 axis in platelet and alleviates cardiac ischemia-reperfusion injury. Melatonin antagonizes mitophagy via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis in cardiac microvasculature. Melatonin activates ALDH2-CGAS-STING1-TBK1 signaling to restore mitophagy in cardiomyocytes of mice with Alzheimer disease. Melatonin activates mitophagy via NR4A1-PRKDC-TP53-BNIP3 axis and improves mitochondrial quality in hepatocytes of nonalcoholic fatty liver disease. |
| H2S | H2S | Cysteine | H2S facilitates PINK1-PRKN mediated mitophagy via sulfhydration of PRKN and USP8. |
| GSH | C10H17N3O6S | Glutamate cysteine glycine | GSH inhibits mitophagy by suppression of Atg32 in yeast. |