Results 41 to 50 of about 3,697 (189)

Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR.

PLoS Biology, 2019
Rapamycin (Rap) and its derivatives, called rapalogs, are being explored in clinical trials targeting cancer and neurodegeneration. The underlying mechanisms of Rap actions, however, are not well understood.
Xiaoli Zhang, Wei Chen, Qiong Gao, Junsheng Yang, Xueni Yan, Han Zhao, Lin Su, Meimei Yang, Chenlang Gao, Yao Yao, Ken Inoki, Dan Li, Rong Shao, Shiyi Wang, Nirakar Sahoo, Fumitaka Kudo, Tadashi Eguchi, Benfang Ruan, Haoxing Xu   +18 more
doaj   +1 more source

ML-SA1, a TRPML1 agonist, induces gastric secretion and gastrointestinal tract inflammation in vivo

STEMedicine, 2020
Background: The effect of ML-SA1, a potent and specific TRPML1 channel agonist, on gastric secretion and subsequent impact to the gastrointestinal (GI) tract of mice was investigated. Methods: Twenty mice were divided into two groups, and respectively
Dan Gong, Jing Hai, Jun Ma, Chen-Xi Wang, Xin-Dan Zhang, Ya-Nan Xiang, Tao Tan, Ya-Nan Liu, Wei Zhang   +8 more
doaj   +1 more source

Induction of lysosomal exocytosis and biogenesis via TRPML1 activation for the treatment of uranium-induced nephrotoxicity

Nature Communications, 2023
Uranium (U) is a well-known nephrotoxicant which forms precipitates in the lysosomes of renal proximal tubular epithelial cells (PTECs) after U-exposure at a cytotoxic dose.
Dengqin Zhong, Ruiyun Wang, Hongjing Zhang, Mengmeng Wang, Xuxia Zhang, Honghong Chen   +5 more
doaj   +1 more source

Regulation of TRPML1 channel activity and inflammatory exosome release by endogenously produced reactive oxygen species in mouse podocytes

Redox Biology, 2021
The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in podocytes has been implicated in the initiation of glomerular inflammation during hyperhomocysteinemia (hHcy).
Guangbi Li, Dandan Huang, Ningjun Li, Joseph K. Ritter, Pin-Lan Li   +4 more
doaj   +1 more source

Human TRPML1 channel structures in open and closed conformations [PDF]

Nature, 2017
Transient receptor potential mucolipin 1 (TRPML1) is a Ca2+-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes. Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder. Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-Å apo structure at pH 7.
Philip, Schmiege, Michael, Fine, Günter, Blobel, Xiaochun, Li   +3 more
openaire   +2 more sources

p53 mitigates the effects of oncogenic HRAS in urothelial cells via the repression of MCOLN1

iScience, 2021
Summary: Inhibition of TRPML1, which is encoded by MCOLN1, is known to deter cell proliferation in various malignancies. Here, we report that the tumor suppressor, p53, represses MCOLN1 in the urothelium such that either the constitutive loss or ectopic ...
Jewon Jung, Han Liao, Shannon A. Coker, Hong Liang, John F. Hancock, Catherine Denicourt, Kartik Venkatachalam   +6 more
doaj   +1 more source

Lysosomal Zn2+ release triggers rapid, mitochondria-mediated, non-apoptotic cell death in metastatic melanoma

Cell Reports, 2021
Summary: During tumor progression, lysosome function is often maladaptively upregulated to match the high energy demand required for cancer cell hyper-proliferation and invasion. Here, we report that mucolipin TRP channel 1 (TRPML1), a lysosomal Ca2+ and
Wanlu Du, Mingxue Gu, Meiqin Hu, Prateeksunder Pinchi, Wei Chen, Michael Ryan, Timothy Nold, Ahmed Bannaga, Haoxing Xu   +8 more
doaj   +1 more source

TRPML1 Controls Mitochondrial Homeostasis and Alleviates Cardiac Hypertrophy by Inhibiting VDAC1 Oligomerization

Engineering
The preservation of mitochondrial homeostasis plays a critical role in preventing the progression of pathological cardiac hypertrophy to heart failure (HF).
Xiuye Zhao, Mingxiu Zhang, Changling Lv, Chunlei Duan, Zhen Chen, Yan Hao, Zhen Liang, Yiping Tao, Hongda Li, Zhenru Wang, Haonan Du, Jiapan Wang, Wenjie Liao, Peifeng Li, Jia Wang, Xueqi He, Yu Zhang, Xinyuan Hao, Hongyu Ji, Yan Zhang, Xingda Li, Ye Yuan, Zhimin Du   +22 more
doaj   +1 more source

Trafficking Deficiency of TMEM175 Variants in Parkinson's Disease Pathogenesis and the Prospects of Precision Medicine

Advanced Science, EarlyView.
This study identifies that the PD‐associated TMEM175‐L156P variant disrupts lysosomal ion channel trafficking by causing aberrant endoplasmic reticulum retention. A “chaperone–agonist” bifunctional small molecule restores TMEM175‐L156P lysosomal localization and channel function, thereby alleviating PD‐relevant cellular phenotypes and highlighting a ...
Ting Luo, Yu He, Shuyao Li, Haoyu Guan, Ruili Cui, Yu Shi, Zhongwen Jiang, Siyu Wang, Xuan Li, Jiyuan Li, Mei Hu, Yupeng Zhou, Beisha Tang, Yanyan Zhang, Zhaobing Gao, Yu Zhou, Zhenhua Liu, Ping Li   +17 more
wiley   +1 more source

Regulation of mTORC1 by lysosomal calcium and calmodulin

eLife, 2016
Blockade of lysosomal calcium release due to lysosomal lipid accumulation has been shown to inhibit mTORC1 signaling. However, the mechanism by which lysosomal calcium regulates mTORC1 has remained undefined.
Ruo-Jing Li, Jing Xu, Chenglai Fu, Jing Zhang, Yujun George Zheng, Hao Jia, Jun O Liu   +6 more
doaj   +1 more source