Response to metal ions
Sub-pathways within Pathway: Response to metal ions :
Response to metal ions:
Though metals such as zinc, copper, and iron are required as cofactors for cellular enzymes they can also catalyze damaging metal substitution or unspecific redox reactions if they are not sequestered. The transcription factor MTF1 directs the major cellular response to zinc, cadmium, and copper. MTF1 activates gene expression to up-regulate genes encoding proteins, such as metallothioneins and glutamate-cysteine ligase (GCLC), involved in sequestering metals. MTF1 represses gene expression to down-regulate genes encoding transporters that import the metals into the cell (reviewed in Laity and Andrews 2007, Jackson et al. 2008, Günther et al. 2012, Dong et al. 2015). During activation MTF1 in the cytosol binds zinc ions and is translocated into the nucleus, where it binds metal response elements in the promoters of target genes. Activation of MTF1 by cadmium and copper appears to be indirect as these metals displace zinc from metallothioneins and the displaced zinc then binds MTF1.
Metallothioneins bind metals and participate in detoxifying heavy metals, storing and transporting zinc, and redox biochemistry.
Metallothioneins bind metals and participate in detoxifying heavy metals, storing and transporting zinc, and redox biochemistry.
Cellular responses to stimuli:
Individual cells detect and respond to diverse external molecular and physical signals. Appropriate responses to these signals are essential for normal development, maintenance of homeostasis in mature tissues, and effective defensive responses to potentially noxious agents (Kultz 2005). It is convenient, if somewhat arbitrary, to distinguish responses to signals involved in development and homeostasis from ones involved in stress responses, and that classification is followed here, with macroautophagy and responses to metal ions classified as responses to normal external stimuli, while responses to hypoxia, reactive oxygen species, and heat, and the process of cellular senescence are classified as stress responses. Signaling cascades are integral components of all of these response mechanisms but because of their number and diversity, they are grouped in a separate signal transduction superpathway in Reactome.