Cellular iron biology
new Biosensor ‘illuminates’ iron regulatory protein activity and fe status
Sangokoya, The FIRE biosensor illuminates iron regulatory protein activity and cellular iron homeostasis, Cell Reports Methods (2024) https://doi.org/10.1016/j.crmeth.2024.100960 (in press)
in print 1/27/25
Iron is essential for life, yet the full context of its regulation in shaping cell fates in stem cells of the early developing mammalian embryo is not well understood. Sangokoya reports a ratiometric biosensor of iron regulatory protein (IRP) activity and cellular iron to advance functional studies at single cell resolution.
MICRORNA FUNCTION IN CELLULAR IRON HOMEOSTASIS
Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin (PLoS Genetics 2013)
cited in selected review(s): Mechanisms controlling cellular and systemic iron homeostasis (Nature Reviews Molecular Cell Biology 2024), A Red Carpet for Iron Metabolism (Cell 2017), Ironing out ferroportin (Cell Metabolism 2015), MicroRNAs: the fine modulators of liver development and function (Liver International 2014)
Cellular iron homeostasis is maintained by a sophisticated system that responds to iron levels and coordinates the expression of targets important for balancing iron export and uptake with intracellular storage and utilization. Ferroportin is the only known cellular iron exporter in mammalian cells and plays a critical role in both cellular and systemic iron balance.
The ability to regulate cellular iron export is of great interest in the search for therapeutic strategies to target:
*conditions affected or regulated by cellular iron concentrations such as infection and immunity in any organ system (pathogen entry and anatimicrobial resistance), mammalian development (effects of dysregulated maternal and/or embryonic iron), and specific organ-based issues (chronic liver disease, liver regeneration, heart disease)
During iron deprivation, repression of ferroportin levels reduces iron export and preserves cellular iron. Although ferroportin translation is known to be repressed by iron regulatory proteins that bind to the 5′UTR (untranslated region), alternative mechanisms that can post-transcriptionally regulate ferroportin had not been previously reported.
*We found that the microRNA miR-485-3p is induced during iron deficiency in human primary cells and cell lines and represses ferroportin by directly targeting its 3′UTR.
*This experimental evidence introduced a new regulatory model in which both iron regulatory proteins and microRNAs are post-transcriptional regulators of ferroportin.
*These findings described a new role for microRNAs in the cellular response to iron.
