Work

ROS and Drp1-mediated mitochondrial fission contributes to the hyposalivation caused by Sjögren’s disease

Year: 2025

Type: article

Abstract: BACKGROUND: Sjögren's disease (SjD) is an autoimmune disorder characterized by sicca syndrome with undetermined roles of reactive oxygen species (ROS) and mitochondrial dynamics in the damaged glands. This study aimed to clarify the roles of ROS and mitochondrial dynamics in SjD-related hyposalivation and explored the therapeutic effect of targeting mitochondrial fission to treat hyposalivation in murine SjD. METHODS: Single-cell sequencing analysis of submandibular glands (SMGs) from mice with SjD was performed. ROS and mitochondrial dynamics and function were evaluated. Mitochondrial division inhibitor-1 (Mdivi-1) was intraductally infused into the SMGs of mice with SjD. The saliva flow rate was measured after intraperitoneal injection of pilocarpine. RESULTS: Single-cell sequencing analysis revealed that oxidative stress damage in SMGs might play a critical role in hyposalivation caused by SjD. Intraperitoneal injection of Mito-TEMPO (a mitochondrion-targeted antioxidant) increased the salivary flow rate in murine SjD. In vitro, Mito-TEMPO preincubation alleviated mitochondrial dysfunction. Furthermore, the increased ROS levels promoted mitochondrial fission and decreased fusion in vivo and in vitro. Dynamin-related protein 1 (Drp1) and its Ser616 site mediated mitochondrial dysfunction in glandular epithelial cells induced by interferon-γ. Finally, Mdivi-1 and Drp1 inhibitor intraductal infused into the SMGs promote the saliva flow rate in SjD mice, accompanied by improvements in glandular mitochondrial function and cell survival. CONCLUSIONS: The elevated ROS in SGECs participates in hyposalivation in SjD. The excess ROS results in the increased mitochondrial fission via Drp1 and its Ser616 site, further worsening mitochondrial dysfunction in glandular cells. Mdivi-1 intraductal infusion significantly can ameliorate hyposalivation in murine models of SjD.

Source: Chinese Medical Journal

DOI: 10.1097/cm9.0000000000003727

Authors: Yu Zhang, Zhihao Du, Shan Zhang, Weixia Chu, Chong Ding, Xiaofeng Shan

Institutions: Peking University, Shanghai Jiao Tong University, Shanghai First People's Hospital

Language: English

Topic: Salivary Gland Disorders and Functions

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,000