Cellular iron sensing and regulation: Nuclear IRP1 extends a classic paradigm.
Biochim Biophys Acta Mol Cell Res
; 1867(7): 118705, 2020 07.
Article
in En
| MEDLINE
| ID: mdl-32199885
ABSTRACT
The classic view is that iron regulatory proteins operate at the post-transcriptional level. Iron Regulatory Protein 1 (IRP1) shifts between an apo-form that binds mRNAs and a holo-form that harbors a [4Fe4S] cluster. The latter form is not considered relevant to iron regulation, but rather thought to act as a non-essential cytosolic aconitase. Recent work in Drosophila, however, shows that holo-IRP1 can also translocate to the nucleus, where it appears to downregulate iron metabolism genes, preparing the cell for a decline in iron uptake. The shifting of IRP1 between states requires a functional mitoNEET pathway that includes a glycogen branching enzyme for the repair or disassembly of IRP1's oxidatively damaged [3Fe4S] cluster. The new findings add to the notion that glucose metabolism is modulated by iron metabolism. Furthermore, we propose that ferritin ferroxidase activity participates in the repair of the IRP1 [3Fe4S] cluster leading to the hypothesis that cytosolic ferritin directly contributes to cellular iron sensing.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Iron Regulatory Protein 1
/
Iron-Regulatory Proteins
/
Iron
/
Iron-Sulfur Proteins
Language:
En
Journal:
Biochim Biophys Acta Mol Cell Res
Year:
2020
Document type:
Article
Affiliation country:
México