The Role of mTOR, Autophagy, Apoptosis, and Oxidative Stress During Toxic Metal Injury

The evolutionary conserved rate-limiting protein kinase, mammalian target of rapamycin (mTOR), controls cellular homeostasis. The two distinct complexes of mTOR can modulate signaling pathways via upstream and downstream regulation. Metal toxicity generates oxidative stress in different cell types forming free radicals by various modifications to DNA bases, enhanced lipid peroxidation, and altered sulfhydryl homeostasis. Autophagy and apoptosis were regarded as the ultimate consequence of metal-induced oxidative stress. Recruitment or repression of these cell death signaling networks by metal insult can lead to up-regulation and/or down-regulation of mTOR protein. The aim of this review is to analyze the oxidative stress, cell death, and mTOR regulatory networks which offer a multitude of targets for toxic metal injury.