Recent research (http://www.ncbi.nlm.nih.gov/pubmed/21726807) has implicated Nitric Oxide (NO) as an important physiological regulator of autophagy. It downregulates the activity of autophagocytic machinery through a few key routes:
1) Prevents phosphorylation of Bcl-2 by JNK-1 (two key proteins). This leaves Bcl-2 activated. Bcl-2 proceeds to bind key autophagy initiation factor Beclin-1 and deactivate it, preventing autophagy initiation.
2) Upregulates mTorC1 which blocks autophagy through a variety of means.
3)Prevents binding of Vps34 with Beclin-1, preventing formation of the inititaion complex.
It mediates these effects (especialy effect #1) mainly through its ability to 'S-nitrosylate' a specific amino acid called Cysteine located in the reactive site of many of these proteins.
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Cysteine s-nitrosylation. the NO reacts with the thiol (HS) group on the cysteine replacing it with a nitrosyl group. |
Hydrogen Sulphide, the chemical I am investigating, has a very similar mode of action to NO! It 's-sulfhydrates' cysteine residues, and in an interesting point, it massively increases the reactivity of the effected cysteine! (http://www.ncbi.nlm.nih.gov/pubmed/19903941)
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Cysteine s-sulfhydration. The hydrogen sulphide reacts with the thiol producing a highly reactive sulpfhydryl group. |
An interesting hypothesis would be that Nitric Oxide and Hydrogen Sulphide work synergysticly to up and down regulate autphagy through interaction with cysteine residues.
We all know theres only one way to find out! . . .
And see what the evidence has to say! =)
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