TRP14 reduces cystine and PTP1B
A recent paper describes a protein TRP14 ( TXNDC17) as essential for reduction of cystine into cysteine.
I’m pretty sure most people who know about transsulfuration pathway think that cysteine mainly appears in the cells via that pathway. But this is not exactly accurate.
Main source of cysteine in the cells is cystine.
When Nrf2 is activated in response to different stressors it leads to increased expression of the cystine-glutamate anti-porter. This anti-porter exports glutamate in exchange for cystine. Cystine is then placed into lysosome, probably to prevent uncontrolled depletion of NADPH. At some point cystine is exported from the lysosome via cystinosin transporter into cytosol.
Then it’s broken down into two cysteine molecules by previously unknown mechanism that included Thioredoxin Reductase (TXNRD1) - a selenoenzyme, by the way. TXNRD uses NADPH as a source of electrons for reduction of its substrates and FAD as a cofactor.
The newly described protein - TRP14 - is the missing piece of this. TRP14 reduces cystine into cysteine, and then TXNRD1 restores TRP14 like it does with many other proteins.
Highlights
- TRP14 is the enzyme that reduces cystine
- Selenium status is essential because it affects ability to reduce cystine
- Cystine import and its reduction is the major source cysteine in the cells
Another interesting finding:
We also found that TRP14 reactivates oxidized protein tyrosine phosphatase PTP1B (Dagnell et al, 2013)