Mitochondrial translocation of DJ-1 is mediated by Grp75: implication in cardioprotection of resveratrol against hypoxia/reoxygenation-induced oxidative stress.
Mitochondrial translocation of DJ-1 is mediated by Grp75: implication in cardioprotection of resveratrol against hypoxia/reoxygenation-induced oxidative stress.
复制标题
DOI：
10.1097/fjc.0000000000000805
复制
发表时间：
2020-01
影响因子：
3
通讯作者：
Tingting Zhou;Xueying Wang;Jiao-e Huang;Yi-Zhang Deng;Lejia Qiu;Haoyue Liu;Xing-Wang Xu;Zhao-Xia Ma;Lei Tang;He-Ping Chen
中科院分区：
文献类型：
--
作者：
Tingting Zhou;Xueying Wang;Jiao-e Huang;Yi-Zhang Deng;Lejia Qiu;Haoyue Liu;Xing-Wang Xu;Zhao-Xia Ma;Lei Tang;He-Ping Chen
Resveratrol (Res) was recently reported to ameliorate hypoxia/reoxygenation (H/R)-caused oxidative stress in H9c2 cardiomyocytes through promoting the mitochondrial translocation of DJ-1 protein and subsequently preserving the activity of mitochondrial complex I. However, it is noteworthy that DJ-1 possesses no mitochondria-targeting sequence. Therefore, how Res induces DJ-1 mitochondrial translocation is an important and interesting question for further exploration. Glucose regulated protein 75 (Grp75), whose N-terminus contains a 51-amino acid long mitochondrial-targeting signal peptide, is a cytoprotective chaperone that partakes in mitochondrial import of several proteins. Here, the contribution of Grp75 to mitochondrial import of DJ-1 by Res was investigated in a cellular model of H/R. Our results showed that Res upregulated the expression of DJ-1 protein, enhanced the interaction of DJ-1 and Grp75, and promoted DJ-1 translocation to mitochondria from cytosol in H9c2 cardiomyocytes undergoing H/R. Importantly, knockdown of Grp75 markedly reduced the interaction of DJ-1 with Grp75 and subsequent DJ-1 mitochondrial translocation induced by Res. Furthermore, Res pretreatment promoted the association of DJ-1 with ND1 and NDUFA4 subunits of complex I, preserved the activity of complex I, decreased mitochondria-derived reactive oxygen species production, and eventually ameliorated H/R-caused oxidative stress damage. Intriguingly, these effects were largely prevented also by siRNA targeting Grp75. Overall, these results suggested that Grp75 interacts with DJ-1 to facilitate its translocation from cytosol to mitochondria, which is required for Res-mediated preservation of mitochondria complex I and cardioprotection from H/R-caused oxidative stress injury.
