Double agents of cell death: novel emerging functions of apoptotic regulators

Area of Science:

• Cellular Biology
• Molecular Biology
• Oncology

Background:

• Apoptosis is a critical regulated cell death process involved in homeostasis and disease.
• Dysregulation of apoptosis is implicated in cancer pathogenesis, necessitating alternative therapeutic approaches.
• Emerging cell death pathways rely on proteins traditionally associated with apoptosis.

Purpose of the Study:

• To review the convergence points between apoptosis and other regulated cell death pathways.
• To identify novel therapeutic strategies for treating apoptosis-refractory cancers.
• To highlight the complex interplay between different cell death mechanisms.

Main Methods:

• Literature review of apoptosis and alternative cell death pathways.
• Analysis of protein functions across various cell death processes.
• Synthesis of current evidence on the interconnectivity of cell death mechanisms.

Main Results:

• Apoptosis proteins are key regulators in non-apoptotic death pathways including necroptosis, autophagy, pyroptosis, mPTP-mediated necrosis, and ferroptosis.
• Dying cells can display characteristics of multiple regulated cell death types simultaneously.
• Significant overlap exists between canonical apoptosis and alternative cell death pathways.

Conclusions:

• The intricate connections between apoptosis and other cell death pathways offer promising avenues for cancer therapy.
• A comprehensive understanding of cell death requires considering the cross-talk between diverse mechanisms.
• Novel therapeutic strategies may exploit the shared regulatory elements of different cell death processes.