Short-term regulation of TSFM level does not alter amyloidogenesis and mitochondrial function in type-specific cells

作者全名：Li, Xiao-Yun; Zhou, Gui-Feng; Xie, Xiong-Yong; Pu, Ya-Lan; -Chen, Xue; Li, Chen-Lu; Yang, Jie; Wang, Lu; Chen, Guo-Jun

作者地址：[Li, Xiao-Yun; Zhou, Gui-Feng; Xie, Xiong-Yong; Pu, Ya-Lan; -Chen, Xue; Li, Chen-Lu; Yang, Jie; Wang, Lu; Chen, Guo-Jun] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Major Neurol & Mental Disorders, Chongqing Key Lab Neurol,Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China

通信作者：Chen, GJ (通讯作者)，Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Major Neurol & Mental Disorders, Chongqing Key Lab Neurol,Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China.

来源：MOLECULAR BIOLOGY REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001197733900004

JCR分区：Q3

影响因子：2.6

年份：2024

卷号：51

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：TSFM; Amyloid precursor protein; Oxidative phosphorylation; Reactive oxygen species; TPM4

摘要：BackgroundMitochondrial Ts translation elongation factor (TSFM) is an enzyme that catalyzes exchange of guanine nucleotides. By forming a complex with mitochondrial Tu translation elongation factor (TUFM), TSFM participates in mitochondrial protein translation. We have previously reported that TUFM regulates translation of beta-site APP cleaving enzyme 1 (BACE1) via ROS (reactive oxygen species)-dependent mechanism, suggesting a potential role in amyloid precursor protein (APP) processing associated with Alzheimer's disease (AD), which led to the speculation that TSFM may regulate APP processing in a similar way to TUFM.Methods and resultsHere, we report that in cultured cells, knockdown or overexpression TSFM did not change protein levels in BACE1 and APP. Besides, the levels of cytoplasmic ROS and mitochondrial superoxide, in addition to ATP level, cell viability and mitochondrial membrane potential were not significantly altered by TSFM knockdown in the short term. Further transcriptome analysis revealed that expression of majority of mitochondrial genes were not remarkably changed by TSFM silencing. The possibility of TSFM involved in cardiomyopathy and cancer development was uncovered using bioinformatics analysis.ConclusionsCollectively, short-term regulation of TSFM level in cultured cells does not cause a significant change in proteins involved in APP processing, levels in ROS and ATP associated with mitochondrial function. Whereas our study could contribute to comprehend certain clinical features of TSFM mutations, the roles of TSFM in cardiomyopathy and cancer development might deserve further investigation.

基金机构：Institute for Brain Science and Disease

基金资助正文：The authors highly appreciate the supporting from the Institute for Brain Science and Disease, Chongqing Medical University for providing flow cytometry analysis supporting in this study.