Proteolysis of mitochondrial calpain-13 in cerebral ischemia-reperfusion injury

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2024-07-01 DOI:10.1016/j.bbrep.2024.101768

Yusaku Chukai , Toru Sudo , Tomokazu Fukuda , Hiroshi Tomita , Eriko Sugano , Taku Ozaki

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Abstract

Calpains are calcium-dependent cysteine proteases activated by intracellular Ca²⁺. Although calpains mainly exist in the cytosol, calpain-13 is present in the mitochondria in mouse brains; however, the enzymatic properties and physiological functions of calpain-13 remain unknown. Hence, in this study, we predicted and evaluated the enzymatic properties of calpain-13. Based on our bioinformatic approaches, calpain-13 possessed a catalytic triad and EF-hand domain, similar to calpain-1, a well-studied calpain. Therefore, we hypothesized that calpain-13 had calpain-1-like enzymatic properties; however, calpain-13 was not proteolyzed in C57BL/6J mouse brains. Subsequently, cerebral ischemia/reperfusion (I/R) injury caused proteolysis of mitochondrial calpain-13. Thus, our study showed that mitochondrial calpain-13 was proteolyzed in the mitochondria of the I/R injured mouse brain. This finding could be valuable in further research elucidating the involvement of calpain-13 in cell survival or death in brain diseases, such as cerebral infarction.

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脑缺血再灌注损伤中线粒体钙蛋白酶-13的蛋白水解作用

钙蛋白酶是由细胞内 Ca2+ 激活的钙依赖性半胱氨酸蛋白酶。虽然钙蛋白酶主要存在于细胞质中，但钙蛋白酶-13 存在于小鼠大脑的线粒体中；然而，钙蛋白酶-13 的酶学特性和生理功能仍然未知。因此，在本研究中，我们预测并评估了钙蛋白酶-13的酶学特性。根据我们的生物信息学方法，钙蛋白酶-13具有催化三元组和EF-手结构域，与研究较多的钙蛋白酶-1相似。因此，我们推测钙蛋白酶-13具有类似于钙蛋白酶-1的酶学特性；然而，钙蛋白酶-13在C57BL/6J小鼠大脑中没有被蛋白水解。随后，脑缺血再灌注（I/R）损伤导致线粒体钙蛋白酶-13蛋白水解。因此，我们的研究表明，线粒体钙蛋白酶-13 在 I/R 损伤小鼠大脑的线粒体中被蛋白水解。这一发现对进一步阐明钙蛋白酶-13在脑梗塞等脑部疾病中参与细胞存活或死亡的研究很有价值。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.