Biology of endoplasmic reticulum stress in the heart.
The endoplasmic reticulum (ER) is a multifunctional intracellular organelle supporting many processes required by virtually every mammalian cell, including cardiomyocytes. It performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, posttranslational modification including N-linked glycosylation, and synthesis of phospholipids and steroids on the cytoplasmic side of the ER membrane, and regulation of Ca(2+) homeostasis. Perturbation of ER-associated functions results in ER stress via the activation of complex cytoplasmic and nuclear signaling pathways, collectively termed the unfolded protein response (UPR) (also known as misfolded protein response), leading to upregulation of expression of ER resident chaperones, inhibition of protein synthesis and activation of protein degradation. The UPR has been associated with numerous human pathologies, and it may play an important role in the pathophysiology of the heart. ER stress responses, ER Ca(2+) buffering, and protein and lipid turnover impact many cardiac functions, including energy metabolism, cardiogenesis, ischemic/reperfusion, cardiomyopathies, and heart failure. ER proteins and ER stress-associated pathways may play a role in the development of novel UPR-targeted therapies for cardiovascular diseases.
Department of Biochemistry, School of Molecular and Systems Medicine, University of Alberta, Edmonton, Alberta, Canada.
Jody
J
Groenendyk
Pradeep Kumar
PK
Sreenivasaiah
Do Han
DH
Kim
Luis B
LB
Agellon
Marek
M
Michalak
D000818:Animals; D001343:Autophagy; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D056811:Unfolded Protein Response
D018832:Molecular Chaperones