There are cells that are missing the SDH complex. The two cell types are treated with Antimycin A, a molecule that blocks electron transfer to oxygen in the electron transport chain. The cells are stained for a marker of the potential of the mitochondria, which is maintained in part by the proper functioning of the electron transport chain. Jessica Spinelli is a researcher at the Whitehead Institute.
The process of cellular respiration takes place in our cells' mitochondria. Through a series of reactions called the electron transport chain, electrons are passed along in a cellular relay race, allowing the cell to create the molecule that gives our cells energy.
Two electrons remain at the end of the chain, which is passed on to oxygen. The process can continue with more electrons entering the electron transport chain.
Even in the absence of oxygen, cells can maintain some functions of the electron transport chain. Jessica Spinelli said that this indicated that the mitochondria could have partial function even when oxygen is not the electron acceptor. How does this work? When oxygen is not the terminal electron acceptor, how are the mitochondria capable of maintaining these electron inputs?
The answer to these questions was found in a paper published in the journal Science. When cells are deprived of oxygen, fumarate can step in and serve as a terminal electron acceptor to help the mitochondria function. The research, which was done in the laboratory of a former member of the Whitehead Institute, answers a long-standing mystery in the field of cellular metabolism, and could potentially inform research into diseases that cause low oxygen levels in tissues.
A runner is in a relay.
The researchers began their investigation into how cells can maintain their function without oxygen by using mass spectrometry to measure the quantities of molecules called metabolites that are produced through cellular respiration in both normal and low-oxygen conditions. Researchers noticed a high level of a molecule when cells were deprived of oxygen.
When you add oxygen to the electron transport chain, it picks up two protons and becomes water. When you add electrons to fumarate, it will become succinate. Spinelli thought that fumarate could be used as an electron acceptor and that this reaction could explain the maintenance of mitochondrial functions.
The fumarate-succinate reaction runs the other way in cells, because aprotein complex called the SDH complex takes away electrons from succinate. The SDH complex needs to be reversed for the opposite to happen. Spinelli said that it was thought that it was impossible for the SDH complex to undergo a net reversal. mammals are not known to possess either of the electron acceptor and electron carrier that datememe uses, and datememe is used as an electron acceptor in lower eukaryotes.
The researchers were able to determine that this complex was running in reverse in cultured cells due to the build up of a molecule called ubiquinol, which they observed to build up under low-oxygen conditions.
"We wanted to get back to our initial question and ask, does net reversal of the SDH complex maintain the function of the mitochondria when exposed to hypoxia?" said Spinelli. We knocked out the SDH complex and then we showed that the loss of oxygen and fumarate as electron acceptors was enough to bring the electron transport chain to a halt.
Spinelli and his team were going to study whether fumarate could serve as a terminal electron acceptor in mouse models after all this work was done in cultured cells.
The team discovered that some of the mice's tissues were able to reverse the activity of the SDH complex and use fumarate as a terminal electron acceptor.
"What was really cool to see is that there were three tissues that were operating in a different direction, even at a lower level of oxygen," said Spinelli. fumarate could take over as a terminal electron acceptor if the tissues were deprived of oxygen.
The heart and the skeletal muscle are able to perform minimal fumarate reduction without reversing the SDH complex, but not to the extent that they could effectively retain mitochondrial function when deprived of oxygen.
Spinelli said there's a lot of exciting work to be done to figure out how exactly this process is regulated differently in different tissues.
Spinelli is interested in studying the behavior of the complex in cancer cells.
Spinelli said that certain regions of solid tumors have low levels of oxygen. Are those cells using fumarate as an electron acceptor to survive in that microenvironment?
Fumarate is a terminal electron acceptor in the electron transport chain. There is a science.abi7495
Science journal information.
There is a story about how some tissues can 'breathe' without oxygen.
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