mTORC1 beyond anabolic metabolism: Regulation of cell death

Area of Science:

• Cellular Biology
• Metabolic Regulation
• Biochemistry

Background:

• The mechanistic target of rapamycin complex 1 (mTORC1) is a key regulator of cellular metabolism, integrating growth factor signals with nutrient and energy availability.
• mTORC1 activation promotes anabolic processes (biosynthesis) while inhibiting catabolic processes (degradation), maintaining metabolic homeostasis.
• Metabolic dysregulation is increasingly recognized as a critical factor in diverse cell death pathways, including apoptosis, pyroptosis, and ferroptosis.

Approach:

• This review synthesizes current knowledge on the intricate relationship between mTORC1 signaling and cell death.
• The focus is on how nutrient availability and cellular signaling converge to modulate mTORC1 activity.
• Specific attention is given to the connection between mTORC1 and ferroptosis, an iron-dependent form of cell death.

Key Points:

• mTORC1 plays a central role in coordinating metabolic pathways that influence cell fate decisions.
• Nutrient sensing pathways directly impact mTORC1 activity, thereby affecting cellular susceptibility to death.
• Ferroptosis, a distinct cell death modality, is significantly influenced by metabolic states regulated by mTORC1.

Conclusions:

• Understanding the interplay between mTORC1 and cell death pathways is crucial for deciphering disease mechanisms.
• Targeting the mTORC1-mediated metabolic control of cell death, particularly ferroptosis, holds promise for novel therapeutic strategies.
• Further research into these molecular connections can pave the way for innovative treatments for various human diseases.