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

Xingzhao Ji; Lingju Chu; Dun Su; Jian Sun; Peng Song; Shengnan Sun; Ying Wang; Qian Mu; Yi Liu; Qiang Wan

doi:10.1016/j.isci.2023.106656

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

iScience. 2023 Apr 14;26(5):106656. doi: 10.1016/j.isci.2023.106656. eCollection 2023 May 19.

Authors

Xingzhao Ji^{1

2

3

4}, Lingju Chu^{1

5}, Dun Su^{1

5}, Jian Sun^{2

3

4}, Peng Song^{2

3

4}, Shengnan Sun^{1

5}, Ying Wang^{2

3

4}, Qian Mu^{2

3

4}, Yi Liu^{2

6

3

4}, Qiang Wan^{1

5}

Affiliations

¹ Center of Cell Metabolism and Disease, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
² Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
³ Shandong Key Laboratory of Infections Respiratory Disease, Jinan, Shandong 250021, China.
⁴ Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China.
⁵ Key Laboratory of Cell Metabolism in Medical and Health of Shandong Provincial Health Commission, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
⁶ Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.

Abstract

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.

Keywords: Bioengineering; Cell engineering; Injury.