MRPL12-ANT3 interaction involves in acute kidney injury via regulating MPTP of tubular epithelial cells

Acute kidney injury (AKI) is a serious disease with no effective treatment. Abnormal opening of mitochondrial permeability transition pore (MPTP) is an important pathological process in ischemia reperfusion injury (IRI), the key factor of AKI. It is essential to elucidate MPTP regulation mechanism. Here, we identified mitochondrial ribosomal protein L7/L12 (MRPL12) specifically binds to adenosine nucleotide translocase 3 (ANT3) under normal physiological conditions, stabilizes MPTP and maintains mitochondrial membrane homeostasis in renal tubular epithelial cells (TECs). During AKI, MRPL12 expression was significantly decreased in TECs, and MRPL12-ANT3 interaction was reduced, leading to ANT3 conformation change, MPTP abnormal opening, and cell apoptosis. Importantly, MRPL12 overexpression protected TECs from MPTP abnormal opening and apoptosis during hypoxia/reoxygenation (H/R). Our results suggest MRPL12-ANT3 axis involves in AKI by regulating MPTP, and MRPL12 could be potential intervention target for treatment of AKI.

Automated summary

Acute kidney injury (AKI) is a serious disease with no effective treatment. Abnormal opening of mitochondrial permeability transition pore (MPTP) is an important pathological process in AKI. MRPL12, a mitochondrial ribosomal protein, plays a crucial role in stabilizing MPTP and maintaining mitochondrial membrane homeostasis in renal tubular epithelial cells (TECs). Reduced expression of MRPL12 in TECs during AKI leads to MPTP abnormal opening and cell apoptosis. MRPL12 overexpression protects TECs from MPTP abnormal opening and apoptosis during hypoxia/reoxygenation (H/R). MRPL12-ANT3 axis could be a potential intervention target for AKI treatment.