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Mitochondrial mechanism links protein folding to heme production and cell energy
Researchers at the University of Cologne have discovered a previously unknown mechanism that links two fundamental processes in mitochondria. The team, led by Julia Racho and Dylan Stobbe under the supervision of Professor Dr. Jan Riemer from the Institute of Biochemistry at the University of Cologne, demonstrated that the oxidative folding of proteins—that is, the process by which proteins acquire their functional three-dimensional structure and additional stabilizing disulfide bonds—is closely linked to the formation of heme. Heme is a vital component of the red blood pigment hemoglobin and is also required for energy production in cells, as well as for many other biological processes. The findings are published in the journal Science Advances.
The study focuses particularly on the enzyme ALR, a protein that enables chemical reactions. It was previously known that ALR keeps another enzyme, MIA40, active. The researchers have now shown that ALR performs another important function: It stabilizes an enzyme called CPOX, which is responsible for a crucial step in the formation of heme. Only through this stabilization can CPOX operate reliably. Without it, the enzyme becomes unstable and heme production is thrown out of balance.
As part of this study, the researchers developed a method for detecting proteins that come into direct contact with ALR during their folding. This enabled them to identify CPOX as a direct partner of ALR for the first time. Further experiments showed that, while CPOX can also function outside mitochondria, heme production is significantly less efficient there. At the same time, chemical byproducts build up, damaging cells and making them more susceptible to what is known as oxidative stress—a form of cell damage caused by highly reactive oxygen compounds.
"Our findings show that oxidative protein folding in mitochondria plays a far greater role than previously thought. Not only does it ensure that proteins adopt their correct shape, but it also directly supports a vital metabolic process," says lead author Julia Racho.
The discovery also provides new insights into why mutations in the ALR gene can lead to rare inherited mitochondrial disorders in which cells' energy supply is disrupted. At the same time, it broadens our existing understanding of the functions of mitochondria: The correct folding of proteins not only serves their own function but also regulates important metabolic processes. Future studies will investigate whether other enzymes are stabilized in a similar way and what significance this mechanism has for human diseases.
Publication details
Julia Racho et al, ALR couples IMS redox and heme biosynthesis beyond the disulfide relay, Science Advances (2026). DOI: 10.1126/sciadv.aed2430
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Citation: Mitochondrial mechanism links protein folding to heme production and cell energy (2026, July 23) retrieved 24 July 2026 from https://phys.org/news/2026-07-mitochondrial-mechanism-links-protein-heme.html
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