2024-09-24 09:45:54
Scientists have shown an important role for sodium in cellular energy generation.
The study was carried out by a group that includes the GENOXPHOS research group of the National Center for Cardiovascular Research (CNIC) and the Center for Biomedical Research Network on Frailty and Healthy Aging (CIBERFES), in Spain all these things, managed by Dr. Jose Antonio Enriquez.
The study has the participation of researchers from the Biomedical Research Network for Cardiovascular Diseases (CIBERCV), the Complutense University of Madrid (UCM), the Hospital Doce de Octubre Biomedical Research Institute and the David Geffen School of Medicine of the University of California. in Los Angeles (UCLA), the latter institution in the United States and the rest in Spain.
The authors of the study have shown that mitochondrial complex I, the one most responsible for cellular energy generation, has a sodium transport function that is essential for cellular energy production.
The discovery of this activity has made it possible to explain molecularly the pathogenicity of Leber hereditary optic neuropathy (LHON), a neurodegenerative disease. It has been shown that it is a specific failure in sodium and proton transport by mitochondrial complex I that causes the cell death that causes Leber hereditary optic neuropathy, the most common mitochondrial genetic disease worldwide. This pathology, described for the first time in 1988, is associated with defects in mitochondrial DNA.
Since Dr. Peter Mitchell developed the chemiosmotic theory in 1961, and won the Nobel Prize in 1978, there have been no significant revisions in this field. According to this process, a proton gradient generates electrical energy in the mitochondria necessary for the production of ATP, the main source of cellular energy. However, new research has identified that sodium, something that was not considered until now, also contributes in this process.
Led by doctors José Antonio Enríquez and Pablo Hernansanz, the researchers used a combination of genetics and different genetic models, showing that the mitochondrial complex I exchanges sodium ions for protons, forming a sodium base. similar to that of protons. This sequence can represent up to half of the mitochondrial membrane potential, is necessary for ATP production.
Jesús Vázquez Cobos, Iván López-Montero, Enrique Calvo Alcocer, Pablo Hernansanz Agustín, Carmen Morales Vidal, José Antonio Enríquez, Rebeca Acín Pérez, Sara Jaroszewicz and José Luis Cabrera Alarcón, members of the research team. (Photo: CNIC)
The mechanism of this mechanism is important for mammalian biology.
Dr. José Antonio Enríquez explained: “By eliminating complex I in mouse models and confirming it in human cells, we noticed that this transport function was lost, while other complexes, such as III or IV, were removed, this function ” that failure in complex I involves direct sodium-proton transport.” Through these experiments, researchers were able to determine that both functions (hydrogenase and sodium-proton) are independent but fundamental to cellular function.
“Our results show that mitochondria have a sodium balance, essential for their function and to combat cellular stress,” said Dr. Pablo Hernansanz.
For his part, Dr. José Antonio Enríquez demonstrated that this process is important for the biology of animals.
For the possibility of designing possible treatments for this pathology, Dr. José Antonio Enríquez said that there are currently drugs capable of mimicking the function of sodium transport through the inner mitochondrial membrane that works well in isolated mitochondria . However, the use of these compounds in patients is problematic due to their highly toxic side effects on sodium transport in the cell membrane. “The challenge for the future is to design a drug that is important in the mitochondria without affecting other parts of the cell,” said Dr. Enríquez.
Furthermore, researchers believe that damage to sodium-proton transport may have implications in other common neurodegenerative diseases other than LHON, such as Parkinson’s disease.
The study is titled “A transmitochondrial sodium gradient controls membrane potential in mammalian mitochondria.” And it was published in the academic journal Cell. (Source: CNIC)
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