A transmitochondrial sodium gradient controls membrane potential in mammalian mitochondria

Hernansanz-Agust?′n et al., A transmitochondrial sodium gradient controls membrane potential in mammalian mitochondria, Cell (2024).        

Credits for Summary: Khyati Shukla Aakash Khurana

This study investigates the role of the mitochondrial Na+/H+ antiporter (mNHE) in regulating mitochondrial function and membrane potential (DJmt) in mammalian cells. The authors focus on how the Na+ gradient, generated by mNHE activity linked to Complex I (CI), is crucial for maintaining mitochondrial bioenergetics. The research particularly highlights the implications of these mechanisms in neuronal physiology and their potential involvement in diseases such as Leber's Hereditary Optic Neuropathy (LHON).

To conduct the study, the researchers utilized various experimental models, including mouse models and cell cultures, to assess mitochondrial function. They employed techniques such as mitochondrial isolation, blue native gel electrophoresis, and confocal microscopy to measure parameters like O2 consumption, mitochondrial membrane potential, and Na+ gradients. The results revealed that CI conducts mNHE activity, which is essential for generating a Na+ gradient across the inner mitochondrial membrane. LHON-associated mutations lead to decreased mNHE activity, impairing mitochondrial ion management and bioenergetics.

The findings suggest that restoring mNHE activity with monensin, a Na+ ionophore, can reverse bioenergetic defects in LHON models, indicating potential therapeutic strategies. The study emphasizes the importance of Na+ gradients in mitochondrial biology and their implications for neuronal health. Overall, this research enhances our understanding of mitochondrial physiology and opens new avenues for exploring treatments for mitochondrial diseases, particularly those affecting neuronal tissues.