Heme, the iron-holding molecule that provides blood its red color, is crucial for all times. Yet, mockingly, it could be quite toxic if not properly handled. Actually, quite a few diseases – from various cancers to cardiovascular diseases – are related to defects in heme homeostasis.

The best way heme is biosynthesized and degraded has been known for many years, but the way it is mobilized from sites of synthesis and storage to be used in cells has not been clear. Researchers on the Georgia Institute of Technology have developed latest tools and approaches to image, monitor, and probe heme in biological systems to review how organisms handle this essential but potentially cytotoxic metabolite. Their findings are published within the journal Nature.

In a collaboration with Zhejiang University and the University of Maryland School of Medicine, the research team discovered a previously uncharacterized protein, HRG-9 (also called TANGO2), that helps to mobilize heme from sites of synthesis or storage to be used in metabolism. The invention of a latest protein that ensures heme is made bio-available may function a latest therapeutic goal in lots of disease contexts – either to limit heme, to starve cells of this essential nutrient, or to cause heme to over accumulate and render it toxic to cells.

Since mutations within the TANGO2 gene cause a hereditary disease characterised by developmental delays and defects in metabolism, our finding that TANGO2 plays a job in heme homeostasis suggests that the event of heme-centered therapies may treat such diseases.”

Amit Reddi, Associate Professor, School of Chemistry at Georgia Tech and co-PI on the paper

The researchers hope that understanding the mechanisms of heme trafficking will provide clues about how such ‘essential toxins’ are safely trafficked throughout the cell. It could also encourage therapeutic strategies to treat diseases related to heme dysregulation, including anemias, porphyrias, and certain neurodegenerative and cardiovascular disorders.

Source:

Georgia Institute of Technology

Journal reference:

Sun, F., et al. (2022) HRG-9 homologues regulate haem trafficking from haem-enriched compartments. Nature. doi.org/10.1038/s41586-022-05347-z.