Autophagy is impaired in cardiac ischemia-reperfusion injury

Accumulating evidence attests to a prosurvival role for autophagy under stress, by facilitating removal of damaged proteins and organelles and recycling basic building blocks, which can be utilized for energy generation and targeted macromolecular synthesis to shore up cellular defenses. These obser...

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Bibliographic Details
Published in:Autophagy 2012-09, Vol.8 (9), p.1394-1396
Main Authors: Ma, Xiucui, Liu, Haiyan, Foyil, Sarah R., Godar, Rebecca J., Weinheimer, Carla J., Diwan, Abhinav
Format: Article
Language:English
Subjects:
Animals
Apoptosis Regulatory Proteins - metabolism
autophagic flux
Autophagic Punctum
Autophagy - genetics
Beclin-1
BECN1
Binding
Biology
Bioscience
Calcium
Cancer
Cell
cell death
Cycle
Gene Regulatory Networks - genetics
ischemia-reperfusion
LAMP2
Landes
Lysosomes - metabolism
Mice
Models, Biological
Myocardial Reperfusion Injury - pathology
Organogenesis
Phagosomes - metabolism
Proteins
reactive oxygen species
Reactive Oxygen Species - metabolism
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Summary:Accumulating evidence attests to a prosurvival role for autophagy under stress, by facilitating removal of damaged proteins and organelles and recycling basic building blocks, which can be utilized for energy generation and targeted macromolecular synthesis to shore up cellular defenses. These observations are difficult to reconcile with the dichotomous prosurvival and death-inducing roles ascribed to macroautophagy in cardiac ischemia and reperfusion injury, respectively. A careful reexamination of 'flux' through the macroautophagy pathway reveals that autophagosome clearance is markedly impaired with reperfusion (reoxygenation) in cardiomyocytes following an ischemic (hypoxic) insult, resulting from reactive oxygen species (ROS)-mediated decline in LAMP2 and increase in BECN1 abundance. This results in impaired autophagy that is 'ineffective' in protecting against cell death with ischemia-reperfusion injury. Restoration of autophagosome clearance and by inference, 'adequate' autophagy, attenuates reoxygenation-induced cell death.
ISSN:1554-8627
1554-8635
DOI:10.4161/auto.21036