Death from within: apoptosis and the secretory pathway

Area of Science:

• Cell Biology
• Molecular Biology
• Apoptosis Research

Background:

• The secretory pathway, comprising the endoplasmic reticulum (ER) and Golgi apparatus, is crucial for protein processing and transport.
• Emerging evidence suggests the secretory pathway's involvement in cellular stress responses and programmed cell death (apoptosis).
• Understanding how the ER and Golgi sense stress and initiate apoptotic signaling is vital for comprehending cell fate decisions.

Purpose of the Study:

• To elucidate the role of the secretory pathway in stress-induced apoptotic signaling.
• To investigate the mechanisms by which ER and Golgi stress trigger recovery or apoptosis.
• To identify the molecular components within the secretory pathway that mediate apoptotic initiation.

Main Methods:

• Analysis of protein cleavage events in ER- and Golgi-resident proteins during stress.
• Investigating the localization of apoptosis-executing machinery to ER and Golgi membranes.
• Studying the impact of inter-organelle trafficking on stress signal integration and cellular response.

Main Results:

• Stress sensing by the ER and Golgi can initiate cellular recovery or, if unsuccessful, trigger apoptosis.
• Cleavage of proteins within the ER and Golgi can signal either repair or apoptosis, and facilitate organelle breakdown.
• Apoptosis initiation from the secretory pathway necessitates the presence of death machinery components on these organelle membranes.
• Intracellular trafficking within the secretory pathway allows for signal integration to determine the appropriate cellular response to stress.

Conclusions:

• The secretory pathway is a critical regulator of stress-induced apoptosis.
• Mechanisms involving protein cleavage and the localization of death machinery within the ER and Golgi are key to this process.
• Inter-compartmental trafficking within the secretory pathway is essential for integrating stress signals and dictating cell fate.