Slc25a21 in cisplatin-induced acute kidney injury: a new target for renal tubular epithelial protection by regulating mitochondrial metabolic homeostasis.
Xin Su, Mi Bai, Yaqiong Shang, Yang Du, Shuang Xu, Xiuli Lin, Yunzhi Xiao, Yue Zhang, Huimei Chen, Aihua Zhang
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引用次数: 0
Abstract
Acute kidney injury (AKI) is a significant global health issue, which is often caused by cisplatin therapy and characterized by mitochondrial dysfunction. Restoring mitochondrial homeostasis in tubular cells could exert therapeutic effects. Here, we investigated Slc25a21, a mitochondrial carrier, as a potential target for AKI intervention. Renal Slc25a21 expression is negatively associated with kidney function in both AKI patients and cisplatin-induced murine models. Sustaining renal expression of Slc25a21 slowed down AKI progression by reducing cellular apoptosis, necroptosis, and the inflammatory response, likely through its regulation of 2-oxoadipate conversion. Slc25a21 is highly expressed in proximal tubular epithelial cells, and its down-regulation contributes to compromised mitochondrial biogenesis and integrity, as well as impaired oxidative phosphorylation. Mechanistically, reduced Slc25a21 in AKI disrupts mitochondrial 2-oxoadipate transport, affecting related metabolites influx and the tricarboxylic acid cycle. These findings demonstrate a previously unappreciated metabolic function of Slc25a21 in tubular cells, and suggest that targeting mitochondrial metabolic homeostasis by sustaining Slc25a21 expression could be a potential novel therapeutic strategy for AKI.
期刊介绍:
Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism.
Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following:
Experimental medicine
Cancer
Immunity
Internal medicine
Neuroscience
Cancer metabolism