The interplay of ROS and the PI3K/Akt pathway in autophagy regulation

Autophagy causes the breakdown of damaged proteins and organelles to their constituent components. The phosphatidylinositol 3-kinase (PI3K) pathway played an important role in regulating the autophagic response of cells in response to changing reactive oxygen species (ROS) levels. The PI3K alpha catalytic subunit inhibits autophagy, while its beta catalytic subunit promotes autophagy in response to changes in ROS levels. The downstream Akt protein acts against autophagy initiation in response to increases in ROS levels under nutrient-rich conditions. Akt acts by activating a mechanistic target of the rapamycin complex 1 (mTORC1) and by arresting autophagic gene expression. The AMP-activated protein kinase (AMPK) protein counteracts the Akt actions. mTORC1 and mTORC2 inhibit autophagy under moderate ROS levels, but under high ROS levels, mTORC2 can promote cellular senescence via autophagy. Phosphatase and tensin homolog (PTEN) protein are the negative regulators of the PI3K pathway, and it has proautophagic activities. Studies conducted on cells treated with flavonoids and ionizing radiation showed that the moderate increase in ROS levels in the flavonoid-treated groups corresponded with higher PTEN levels and lowered Akt levels leading to a higher occurrence of autophagy. In contrast, higher ROS levels evoked by ionizing radiation caused a lowering of the incidence of autophagy.

Automated summary

Autophagy is regulated by the PI3K pathway and Akt protein in response to changing ROS levels. Flavonoids and ionizing radiation can modulate autophagy by affecting PTEN and Akt protein levels, depending on the levels of ROS induced.