Scientists discover how mitochondria import antioxidants

Date:
November 4, 2021
Source:
Rockefeller University
Summary:
A new finding offers researchers a direct way to investigate
oxidative stress and its damaging effects in aging, cancer and
other diseases.



FULL STORY ==========================================================================
Many of the processes that keep us alive also put us at risk. The
energy- producing chemical reactions in our cells, for example, also
produce free radicals -- unstable molecules that steal electrons from
other molecules. When generated in surplus, free radicals can cause
collateral damage, potentially triggering malfunctions such as cancer, neurodegeneration, or cardiovascular disease.


========================================================================== Cells solve this problem by synthesizing antioxidants, compounds that neutralize free radicals. In a new study, Rockefeller scientists identify
a key molecule that ferries glutathione, the body's major antioxidant,
into the cell's mitochondria, where free radicals are produced en
masse. The discovery, published in Nature, opens new possibilities for investigating oxidative stress and its damaging effects.

"With the potential transporter identified, we can now control the
amount of glutathione that enters mitochondria and study oxidative
stress specifically at its source," says Kivanc, Birsoy, Chapman Perelman Assistant Professor at The Rockefeller University.

The shuttle into the mitochondria To avoid oxidative stress, cells
need to properly balance the levels of free radicals and antioxidants
within their mitochondria, where energy production happens. Because
glutathione is produced outside of mitochondria, in the cell's cytosol,
the scientists wanted to know how it gets transported into these tiny powerhouses in the first place.

To shed light on this process, Birsoy's team monitored protein expression
in cells in response to glutathione's levels. "We hypothesized that
glutathione is shuttled by a transporter protein whose production is
regulated by glutathione," Birsoy says. "So if we lower the levels
of glutathione, the cell should compensate by upregulating the
transporter protein." The analysis pointed to SLC25A39, a protein in
the mitochondrial membrane whose function was hitherto unknown. The
researchers found that blocking SLC25A39 reduced glutathione inside the mitochondrion, without affecting its levels elsewhere in the cell. Other experiments showed that mice cannot survive without SLC25A39. In animals engineered to lack this protein, red blood cells quickly die by oxidative stress due to their failure to bring glutathione into mitochondria.

The identification of the transporter may lead to a better understanding
of a variety of disease pathways linked to oxidative stress, including
those involved in aging and neurodegeneration. "These conditions could potentially be treated or prevented by stimulating antioxidant transport
into mitochondria," Birsoy says.

Moreover, the team is now exploring whether SLC25A39 might hold promise
as a drug target for cancer, by helping to induce fatal oxidative stress
in tumor cells. "In cancer, we would want to prevent antioxidants from
getting into mitochondria, and the transporter protein may be our way
to do that," Birsoy says.

========================================================================== Story Source: Materials provided by Rockefeller_University. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Ying Wang, Frederick S. Yen, Xiphias Ge Zhu, Rebecca C. Timson, Ross
Weber, Changrui Xing, Yuyang Liu, Benjamin Allwein, Hanzhi Luo,
Hsi-Wen Yeh, So/ren Heissel, Gokhan Unlu, Eric R. Gamazon, Michael
G. Kharas, Richard Hite, Kıvanc, Birsoy. SLC25A39 is necessary
for mitochondrial glutathione import in mammalian cells. Nature,
2021; 599 (7883): 136 DOI: 10.1038/s41586-021-04025-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211104162556.htm

--- up 9 weeks, 8 hours, 25 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)