Autophagy function and its relationship to pathology, clinical applications, drug metabolism and toxicity.
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.
National Center for Toxicological Research, US FDA, Division of Genetic and Molecular Toxicology, Jefferson, AR, 72079, USA.
Dayton M
DM
Petibone
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, AR, 72204, USA.
Waqar
W
Majeed
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, AR, 72204, USA.
Daniel A
DA
Casciano
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D035843:Biomedical Research / Q000379:methods*; D002318:Cardiovascular Diseases / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009369:Neoplasms / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000473:pathology; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations
amphiphilic cationic drugs; autophagy; carcinogenesis; clinical applications; disease progression; drug toxicity; phospholipidosis