Biology Reference
In-Depth Information
4.2.1. ERAD
239
4.2.2. Autophagy
241
4.2.3. Examples of ER Proteins Degraded by ERAD and/or Autophagy
242
4.3. ER-phagy
242
5. UPRandCellMetabolism
243
5.1. UPR-MediatedRegulationofMasterMetabolicSwitches
244
5.2. UPRRegulationofLipidMetabolism
246
5.3. UPRRegulationofCarbohydrateHomeostasis
247
5.4. ERStress-ModulatedMitochondrialMetabolism
247
6. UPRandPathologies
249
6.1. UPRandDiabetes
250
6.2. UPRandCardiovascularDiseases
252
6.2.1. Ischemia/Reperfusion
252
6.2.2. Cardiac Hypertrophy and Heart Failure
255
6.3. UPRandNeurodegeneration
257
6.4. UPRandCancer
260
6.4.1. UPR in Tumor Cell Survival
260
6.4.2. UPR as an Adaptive State in Cancer
263
6.4.3. ER-Mitochondria Connection
264
6.4.4. Therapeutic Strategies Based on Suppressing the UPR
266
6.4.5. UPR in Tumor Cell Death
266
7. ConclusionandPerspectives
268
Abstract
Theendoplasmicreticulum(ER)isadynamicintracellularorganellewithmultiplefunc-
tions essential for cellular homeostasis, development, and stress responsiveness. In
response tocellularstress,awell-establishedsignalingcascade, theunfoldedprotein
response (UPR), is activated. This intricate mechanism is an important means of re-
establishingcellularhomeostasisandalleviatingtheincitingstress.Now,emergingevi-
dencehasdemonstratedthattheUPRinfluencescellularmetabolismthroughdiverse
mechanisms,includingcalciumandlipidtransfer,raisingtheprospectofinvolvement
oftheseprocessesinthepathogenesisofdisease,includingneurodegeneration,can-
cer,diabetesmellitusandcardiovasculardisease.Here,wereviewthedistinctfunctions
oftheERandUPRfromametabolicpointofview,highlightingtheirassociationwith
prevalentpathologies.
1. INTRODUCTION
Our understanding of cellular reticulum began in 1945 when it was
first described as a “lace-like” structure in the ground substance of cultured
cells and examined in toto by electron microscopy. The term “endoplas-
mic reticulum” (ER) was coined in 1952 by Porter & Kallman to describe
 
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