Autophagy function and its relationship to pathology, clinical applications, drug metabolism and toxicity

Abstract

Autophagy is a cellular process that facilitates nutrient turnover and removal of expended macromolecules and organelles to maintain homeostasis. The recycling of cytosolic macromolecules and damaged organelles by autophagosomes occurs through the lysosomal degradation pathway. Autophagy can also be upregulated as a prosurvival pathway in response to stress stimuli such as starvation, hypoxia or cell damage. Over the last two decades, there has been a surge in research revealing the basic molecular mechanisms of autophagy in mammalian cells. A corollary of an advanced understanding of autophagy has been a concurrent expansion of research into understanding autophagic function and dysfunction in pathology. Recent studies have revealed a pivotal role for autophagy in drug toxicity, and for utilizing autophagic components as diagnostic markers and therapeutic targets in treating disease and cancer. In this review, advances in understanding the molecular basis of mammalian autophagy, methods used to induce and evaluate autophagy, and the diverse interactions between autophagy and drug toxicity, disease progression and carcinogenesis are discussed. Copyright © 2016 John Wiley & Sons, Ltd.

ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells

“…Autophagy is a regulated cellular self-eating process which degrades and recycles dysfunctional cellular components (Petibone et al 2017). Accumulating evidence suggests that the interplay of autophagy and oxidative stress is involved in many human diseases and toxicant/drug-induced cellular responses (Filomeni et al 2015; Navarro-Yepes et al 2014; Petibone et al 2017).…”

“…Accumulating evidence suggests that the interplay of autophagy and oxidative stress is involved in many human diseases and toxicant/drug-induced cellular responses (Filomeni et al 2015; Navarro-Yepes et al 2014; Petibone et al 2017). Increased oxidative stress can induce autophagy and apoptosis, and both oxidative stress and autophagy are important factors in determining cell fate (death/survival) (Pallichankandy et al 2015; Zhang et al 2015a).…”

Autophagy as a Physiological Response of the Body to Starvation

“…In mammalian cells, survival responses are mainly dependent on hormonal and neuronal deregulations from stress signals. Mammalian cells respond to starvation by activating lipolysis and proteolysis, which are regulated by autophagic activation pathways upon nutrient deprivation (Hosokawa et al 2009;Petibone et al 2017). Activation of lipolysis is required to provide fatty acids through the breakdown of triacylglycerols as an energy source for different tissues and organs during nutrient deprivation (Cockburn and Coore 1995;Angelini et al 2016).…”

Huaier suppresses proliferative and metastatic potential of prostate cancer PC3 cells via downregulation of Lamin�B1 and induction of autophagy

“…In the present study we determined the effect of Huaier on autophagy in PC3 cells. Observation of autophagosomes and other related subcellular structures in the cytoplasm with transmission electron microscope is widely used for autophagy assessment (22,28,29). Ultrastructural changes of PC3 cells treated with Huaier were observed by transmission electron microscope.…”