Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling

Area of Science:

• Cellular Biology
• Molecular Signaling
• Biochemistry

Background:

• Mammalian target of rapamycin (mTOR) and endoplasmic reticulum (ER) stress (unfolded protein response, UPR) pathways regulate critical cellular functions.
• Recent research reveals significant crosstalk between mTOR and ER stress signaling.
• These interactions impact fundamental cell biology and drug discovery.

Purpose of the Study:

• To review the current understanding of the intersections between mTOR and ER stress pathways.
• To highlight the complex regulatory relationships, including both enhancement and antagonism.
• To explore potential therapeutic implications of targeting these crosstalks.

Main Methods:

• Literature review of studies investigating mTOR and ER stress signaling.
• Analysis of molecular mechanisms linking mTOR complex 1 (mTORC1) and ER stress.
• Examination of feedback loops involving Akt signaling.

Main Results:

• mTORC1 signaling is modulated by ER stress, acting both upstream and downstream.
• Prolonged ER stress can promote apoptosis by inhibiting Akt via mTORC1 feedback.
• Chronic ER stress also impairs Akt activation by mTOR complex 2.

Conclusions:

• The interplay between mTOR and ER stress is intricate, affecting cell survival and metabolism.
• Targeting the crosstalk between these pathways offers promising therapeutic avenues.
• Further research is needed to fully elucidate these interactions for clinical applications.