Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival

Authors

Juliana Navarro-Yepes, University of Nebraska-Lincoln
Michaela Burns, University of Nebraska-Lincoln
Anandhan Annadurai, University of Nebraska-LincolnFollow
Oleh Khalimonchuk, University of Nebraska-LincolnFollow
Luz Maria del Razo, CINVESTAV-IPN, Mexico City, Mexico
Betzabet Quintanilla-Vega, CINVESTAV–IPN, Mexico City, Mexico
Aglaia Pappa, Democritus University of Thrace
Mihalis I. Panayiotidis, Heriot-Watt University
Rodrigo Franco, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2014

Citation

Antioxid. Redox Signal. 21, 66–85.

Comments

Copyright 2014, Mary Ann Liebert, Inc. Used by permission.

Abstract

Significance: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent Advances: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. Critical Issues: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. Future Directions: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders.