跳至主要内容

The targeted antioxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

Author：Esther M. Gottwald, Michael Duss, Milica Bugarski, Dominik Haenni, Claus D. Schuh, Ehud M. Landau, Andrew M. Hall   《Physiological Reports》

ABSTRACTS
Kidney proximal tubules (PTs) contain a high density of mitochondria, which are required to generate ATP to power solute transport. Mitochondrial dysfunction is implicated in the pathogenesis of numerous kidney diseases. Damaged mitochondria are thought to produce excess reactive oxygen species (ROS), which can lead to oxidative stress and activation of cell death pathways. MitoQ is a mitochondrial targeted antioxidant that has shown promise in preclinical models of renal diseases. However, recent studies in nonkidney cells have suggested that MitoQ might also have adverse effects. Here, using a live imaging approach, and both in vitro and ex vivo models, we show that MitoQ induces rapid swelling and depolarization of mitochondria in PT cells, but these effects were not observed with SS31, another targeted antioxidant. MitoQ consists of a lipophilic cation (Tetraphenylphosphonium [TPP]) joined to an antioxidant component (quinone) by a 10carbon alkyl chain, which is thought to insert into the inner mitochondrial membrane (IMM). We found that mitochondrial swelling and depolarization was also induced by dodecyltriphenylphosphomium (DTPP), which consists of TPP and the alkyl chain, but not by TPP alone. Surprisingly, MitoQinduced mitochondrial swelling occurred in the absence of a decrease in oxygen consumption rate. We also found that DTPP directly increased the permeability of artificial liposomes with a cardiolipin content similar to that of the IMM. In summary, MitoQ causes mitochondrial swelling and depolarization in PT cells by a mechanism unrelated to antioxidant activity, most likely because of increased IMM permeability due to insertion of the alkyl chain.
SCREENSHOT

RELATED PRODUCTS
 SS31
CHAINING
https://physoc.onlinelibrary.wiley.com/doi/abs/10.14814/phy2.13667
标签：

评论

发表评论

此博客中的热门博文

A Quasi-direct LC-MS/MS-based Targeted Proteomics Approach for miRNA Quantification via a Covalently Immobilized DNA-peptide Probe

Author：Liang Liu, Qingqing Xu, Shuai Hao & Yun Chen     《Scientific Reports》 ABSTRACTS MicroRNAs (miRNAs) play a vital role in regulating gene expression and are associated with a variety of cancers, including breast cancer. Their distorted and unique expression is a potential marker in clinical diagnoses and prognoses. Thus, accurate determination of miRNA expression levels is a prerequisite for their applications. However, the assays currently available for miRNA detection typically require pre-enrichment, amplification and labeling steps, and most of the assays are only semi-quantitative. Therefore, we developed a quasi-direct liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics approach to quantify target miRNA by innovatively converting the miRNA signal into the mass response of a reporter peptide  via  a covalently immobilized DNA-peptide probe. Specifically, the probe containing the targeted proteomics-...
发表评论
阅读全文

Preparation of an antimicrobial surface by direct assembly of antimicrobial peptide with its surface binding activity

Author：Junjian Chen, Yuchen Zhu, Yancheng Song, Lin Wang,  Jiezhao Zhan, Jingcai He, Jian Zheng, Chunting Zhong, Xuetao Shi, Sa Liu, Li Ren and Yingjun Wang     《Journal of Materials Chemistry B》 ABSTRACTS Antimicrobial peptides (AMPs) are a broad prospect for clinical application against bacterial infections of biomaterials. However, a bottleneck exists as there is a lack of simple technology to prepare AMPs on biomaterials with sufficient activity, as the activity of AMP is dependent on the correct orientation on the biomaterial. In the present study, based on the conventional AMP (Tet213: KRWWKWWRRC) and surface binding peptide (SKHKGGKHKGGKHKG), we designed an Anchor-AMP that could be directly assembled onto the surface of the biomaterial and also showed excellent antimicrobial activity. By characterizing the surface using a quartz crystal microbalance with dissipation (QCM-D), contact angle, atom force microscopy (AFM) and X-ray photoelectron spectr...
发表评论
阅读全文

Mutational analysis of the extracellular disulphide bridges of the atypical chemokine receptor ACKR3/CXCR7 uncovers multiple binding and activation modes for its chemokine and endogenous non-chemokine agonists

Author：Martyna Szpakowska, Max Meyrath, Nathan Reynders,  Manuel Counson, Julien Hanson, Jan Steyaert, Andy Chevigné     《Biochemical Pharmacology》 ABSTRACTS The atypical chemokine receptor ACKR3/CXCR7 plays crucial roles in numerous physiological processes but also in viral infection and cancer. ACKR3 shows strong propensity for activation and, unlike classical chemokine receptors, can respond to chemokines from both the CXC and CC families as well as to the endogenous peptides BAM22 and adrenomedullin. Moreover, despite belonging to the G protein coupled receptor family, its function appears to be mainly dependent on β-arrestin. ACKR3 has also been shown to continuously cycle between the plasma membrane and the endosomal compartments, suggesting a possible role as a scavenging receptor. So far, the molecular basis accounting for these atypical binding and signalling properties remains elusive. Noteworthy, ACKR3 extracellular domains bear three  di...
发表评论
阅读全文