TRPML1 and TFEB, an Intimate Affair.
Handb Exp Pharmacol
; 278: 109-126, 2023.
Article
em En
| MEDLINE
| ID: mdl-35879578
ABSTRACT
Ca2+ is a universal second messenger that plays a wide variety of fundamental roles in cellular physiology. Thus, to warrant selective responses and to allow rapid mobilization upon specific stimuli, Ca2+ is accumulated in organelles to keep it at very low levels in the cytoplasm during resting conditions. Major Ca2+ storage organelles include the endoplasmic reticulum (ER), the mitochondria, and as recently demonstrated, the lysosome (Xu and Ren, Annu Rev Physiol 7757-80, 2015). The importance of Ca2+ signaling deregulation in human physiology is underscored by its involvement in several human diseases, including lysosomal storage disorders, neurodegenerative disease and cancer (Shen et al., Nat Commun 3731, 2012; Bae et al., J Neurosci 3411485-11503, 2014). Recent evidence strongly suggests that lysosomal Ca2+ plays a major role in the regulation of lysosomal adaptation to nutrient availability through a lysosomal signaling pathway involving the lysosomal Ca2+ channel TRPML1 and the transcription factor TFEB, a master regulator for lysosomal function and autophagy (Sardiello et al., Science 325473-477, 2009; Settembre et al., Science 3321429-1433, 2011; Medina et al., Nat Cell Biol 17288-299, 2015; Di Paola et al., Cell Calcium 69112-121, 2018). Due to the tight relationship of this lysosomal Ca2+ channel and TFEB, in this chapter, we will focus on the role of the TRPML1/TFEB pathway in the regulation of lysosomal function and autophagy.
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Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article