ER stress and its functional link to mitochondria: role in cell survival and death

JD Malhotra, RJ Kaufman - Cold Spring Harbor …, 2011 - cshperspectives.cshlp.org
JD Malhotra, RJ Kaufman
Cold Spring Harbor perspectives in biology, 2011cshperspectives.cshlp.org
The endoplasmic reticulum (ER) is the primary site for synthesis and folding of secreted and
membrane-bound proteins. Proteins are translocated into ER lumen in an unfolded state
and require protein chaperones and catalysts of protein folding to assist in proper folding.
Properly folded proteins traffic from the ER to the Golgi apparatus; misfolded proteins are
targeted to degradation. Unfolded protein response (UPR) is a highly regulated intracellular
signaling pathway that prevents accumulation of misfolded proteins in the ER lumen. UPR …
The endoplasmic reticulum (ER) is the primary site for synthesis and folding of secreted and membrane-bound proteins. Proteins are translocated into ER lumen in an unfolded state and require protein chaperones and catalysts of protein folding to assist in proper folding. Properly folded proteins traffic from the ER to the Golgi apparatus; misfolded proteins are targeted to degradation. Unfolded protein response (UPR) is a highly regulated intracellular signaling pathway that prevents accumulation of misfolded proteins in the ER lumen. UPR provides an adaptive mechanism by which cells can augment protein folding and processing capacities of the ER. If protein misfolding is not resolved, the UPR triggers apoptotic cascades. Although the molecular mechanisms underlying ER stress-induced apoptosis are not completely understood, increasing evidence suggests that ER and mitochondria cooperate to signal cell death. Mitochondria and ER form structural and functional networks (mitochondria-associated ER membranes [MAMs]) essential to maintain cellular homeostasis and determine cell fate under various pathophysiological conditions. Regulated Ca2+ transfer from the ER to the mitochondria is important in maintaining control of prosurvival/prodeath pathways. We discuss the signaling/communication between the ER and mitochondria and focus on the role of the mitochondrial permeability transition pore in these complex processes.
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