TMEM74 (Transmembrane protein 74), a lysosome transmembrane protein, induces cell autophagy. Knockdown of TMEM74 abolished EBSS-induced autophagy. BIK, belonging to BOP (BH3-only protein) protein family, has been reported to induce cell apoptosis. Autophagy and apoptosis, as different pathways regulated by extra- or intra-cellular signals precisely, both play a crucial role in processes of intra-cellular substrates degradation, energy metabolism and cell survival. However, the relationship between autophagy and apoptosis still remains elusive. To elucidate the putative new relationship and further identify the function of TMEM74, we performed the study mainly using co-immunoprecipitation, immunoblotting, fluorescent location and basic cell biologic experimental techniques. In the present study, for the first time, it is demonstrated that autophagy-related protein TMEM74 co-localizes with apoptosis-related protein BIK in subcellular organelles. The data indicated that TMEM74 associates with BIK via TM domains of TMEM74 and BH3 domain of BIK. Further investigations revealed that TMEM74 inhibits BIK-induced apoptosis by interacting with BIK, as evidenced by the results that autophagosome formation inhibitor could not block the inhibition effect completely. On the contrary, knockdown of TMEM74 and the TM domain-deficient mutant led to deprivation of the function. Overall, the results revealed the autophagy modulator TMEM74 interrelates with apoptosis inducer BIK and inhibits its function, which provides a novel crosstalk point between autophagy and apoptosis to enlarge our understanding of the programmed cell death.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.cellsig.2017.04.005 | DOI Listing |
CNS Neurosci Ther
January 2025
Department of Neurology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
Objective: This study aims to investigate how the E3 ubiquitin ligase LITAF influences mitochondrial autophagy by modulating MCL-1 ubiquitination, and its role in the development of epilepsy.
Methods: Employing single-cell RNA sequencing (scRNA-seq) to analyze brain tissue from epilepsy patients, along with high-throughput transcriptomics, we identified changes in gene expression. This was complemented by in vivo and in vitro experiments, including protein-protein interaction (PPI) network analysis, western blotting, and behavioral assessments in mouse models.
Glaucoma is a leading cause of irreversible blindness, often associated with elevated intraocular pressure (IOP) due to trabecular meshwork (TM) dysfunction. Diabetes mellitus (DM) is recognized as a significant risk factor for glaucoma; however, the molecular mechanisms through which hyperglycemia affects TM function remain unclear. This study investigated the impact of high glucose on gene expression in human TM (HTM) cells to uncover pathways that contribute to TM dysfunction and glaucoma pathogenesis under diabetic conditions.
View Article and Find Full Text PDFClin Transl Med
January 2025
Key Laboratory For Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China.
Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex condition characterized by metabolic dysfunction and myocardial lipotoxicity. The roles of PTEN-induced kinase 1 (PINK1) and peroxiredoxin-2 (Prdx2) in HFpEF pathogenesis remain unclear.
Objective: This study aimed to investigate the interaction between PINK1 and Prdx2 to mitigate cardiac diastolic dysfunction in HFpEF.
J Adv Res
January 2025
College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China. Electronic address:
Introduction: Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!