Work

Nitrate maintains mitochondrial membrane integrity by increasing Sialin-FKBP8 granules via liquid-liquid-phase separation

Year: 2025

Type: article

Abstract: Mitochondria, the metabolic centers of cells, are crucial for both health regulation and disease progression. Mitochondrial membrane disruption and mitochondrial dysfunction are key mechanisms in various diseases, as are salivary gland damage caused by irradiation (IR). Our previous study suggested that nitrate has preventive effects on mitochondrial dysfunction and IR-induced salivary gland damage. However, the mechanism remains unclear. In the present study, supplementation with nitrate significantly reduced mitochondrial damage to salivary epithelial cells in the context of IR-induced salivary gland damage in vivo and cellular injury to human salivary gland cells (HSGs) in vitro. Nitrate alleviated mitochondrial membrane damage in salivary epithelial cells mainly by maintaining the integrity of the mitochondrial membrane. Mechanistically, nitrate upregulates the expression of the nitrate transporter protein Sialin in salivary epithelial cells. Sialin can bind FK506-binding protein 8 (FKBP8) and form Sialin‒FKBP8 granules via liquid‒liquid phase separation, which anchor to the mitochondrial outer membrane and maintain the integrity of the mitochondrial membrane. Overall, the present study is the first to identify the mechanism by which nitrate protects against damage to the mitochondrial membrane and provides an effective strategy for preventing IR-induced damage and other diseases related to mitochondrial damage.

Source: Redox Biology

DOI: 10.1016/j.redox.2025.103901