Zhejiang University recently released a Nature paper: TANGO2 can be used as a target for studying iron-rich blood molecules

Heme is the iron molecule that maintains the red color of the blood and is necessary for
life.
Ironically, however, it can be quite toxic if not handled properly
.
In fact, many diseases — from various cancers to cardiovascular diseases — are associated
with defects in heme homeostasis.

How heme biosynthesizes and degrades has been known for decades, but how it is mobilized from synthetic sites and storage for use in cells is unclear
.
Professor Caiyong Chen's team from the School of Life Sciences, Zhejiang University, published a research paper in the top international journal Nature to reveal the important mechanism of
intracellular heme transport.
The study found a family of heme chaperones whose members HRG-9, HRG-10 and TANGO2 transport heme to heme storage sites or synthetic sites for use
at other subcellular sites.
Nature published a research brief in the same period, presenting and commenting
on the findings.

Sun Fengxiu and Zhao Zhenzhen, graduate students in Chen Caiyong's laboratory, College of Life Sciences, Zhejiang University, are the first authors of this paper, and Chen Caiyong is the corresponding author
.
Shen Shuaiqi, Zhou Yu and other students from the School of Life Sciences of Zhejiang University, as well as Amit Reddi Lab at Georgia Institute of Technology and Iqbal Hamza Lab at the University of Maryland participated in the work
.

In collaboration with Zhejiang University and the University of Maryland School of Medicine, the team discovered a previously uncharacterized protein, HRG-9 (also known as TANGO2), which helps mobilize heme from the location of synthesis or storage for metabolism
.
The discovery of a new protein that ensures heme is bioavailable could become a new therapeutic target in many diseases — either restricting heme so that cells lose this essential nutrient or leading to excessive accumulation of heme that makes it toxic
to cells.

Through analysis, Chen Caiyong's laboratory found that among the organisms that can synthesize heme, there is a gene similar to hrg-9 called TANGO2
.
The gene was originally thought to be involved in
protein secretion and Golgi structure.

Using a variety of research systems and experimental methods, the researchers found that TANGO2 in yeast, zebrafish and mammals can also transport heme
.
In the cells of these organisms, TANGO2 transports heme directly from the mitochondria, the "factory" that makes heme, to facilitate the utilization
of heme.

"Because mutations in the TANGO2 gene lead to a genetic disorder characterized by developmental delays and metabolic defects, we found that TANGO2 plays a role in heme homeostasis, suggesting that the development of heme-centric therapies may treat this class of diseases.
"

The researchers hope that understanding the mechanism of heme transport could provide clues
to how this "essential toxin" is safely transported within cells.
It can also inspire treatment strategies for conditions associated with heme imbalance, including anemia, porphyria, and certain neurodegenerative and cardiovascular diseases
.