The VDAC3/DHODH Axis Ameliorates Sepsis-induced Myocardial Injury by Regulating Ferroptosis

作者：Jiali Wang, Fan Zhang, C J Tan, Nana Wang, Xuexia Xia, Yun Ye, Yue Cao, Xin Huang, Zhenjiang Bai, He Zhao, Ling Sun, Qiuqin Xu, Huiting Zhou, Jie Huang · 发表于：Frontiers in Bioscience-Landmark · 年份：2025 · DOI：10.31083/fbl39559 · 被引用次数：5 · 研究领域：Ferroptosis and cancer prognosis、Immune cells in cancer、Mitochondrial Function and Pathology

Background: Sepsis-induced myocardial injury (SIMI) represents a major contributor to prolonged hospitalization in intensive care units (ICUs) and is associated with increased mortality rates. Mitochondria serve as the primary energy source for cardiomyocytes and are also essential for various other cell functions. The essential voltage-dependent anion channel 3 (VDAC3) protein located in the outer mitochondrial membrane plays a crucial role in preserving mitochondrial homeostasis by controlling metabolite transport and the shape of cristae. However, the precise mechanism by which VDAC3 is involved in SIMI remains unclear. This study aimed to explore the function and mechanism of VDAC3 in SIMI pathogenesis, with a particular emphasis on its regulatory role in ferroptosis. Methods: Lipopolysaccharide (LPS)-treated HL-1 cardiomyocytes (a murine cardiomyocyte cell line) were used to construct an in vitro myocardial injury model, and mice were used to establish a cecal ligation and puncture (CLP)-induced in vivo myocardial injury model. Transmission electron microscopy (TEM) was employed to evaluate the mitochondrial ultrastructure in cardiac tissues, while hematoxylin-eosin (H&E) staining was used to assess histopathological alterations. Echocardiography was used to evaluate the structural and functional characteristics of the heart. Integrated transcriptome and proteomic studies were performed to identify differentially expressed genes. VDAC3 expression levels, inflammatory...