Linking cellular stress responses to systemic homeostasis.

Area of Science:

• Cellular stress response and systemic signaling in mammals.
• Intercellular communication in maintaining organismal homeostasis.

Background:

• Intracellular stress responses (DNA damage, unfolded protein response, mitochondrial stress, autophagy) are well-studied.
• Limited understanding exists regarding signals from stressed cells that coordinate organism-wide adaptive responses.

Purpose of the Study:

• To investigate the nature and implications of signals emanating from stressed mammalian cells.
• To understand how these signals contribute to coordinated tissue, organ, and organismal responses.

Main Methods:

• Review and synthesis of accumulated evidence on cellular stress response pathways.
• Analysis of signaling mechanisms involving cell surface changes, soluble factors, and microvesicles.
• Examination of the link between intracellular stress responses and systemic signaling.

Main Results:

• Intracellular stress responses and cell death/senescence mechanisms are coupled with signal generation.
• These signals involve alterations in cell surface, secreted factors, and microvesicles.
• Signals generally support systemic homeostasis but can also lead to maladaptation and disease.

Conclusions:

• Stressed cells actively communicate with their environment to orchestrate systemic adaptive responses.
• While crucial for homeostasis, these stress-induced signals have a dual role, potentially contributing to pathology.