The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death

Area of Science:

• Cellular Biology
• Molecular Biology
• Immunology

Background:

• Apoptosis is a regulated cell death executed by caspase-3/7, activated by upstream caspases in response to signals.
• Necroptosis, pyroptosis, and ferroptosis are distinct regulated cell death pathways triggered by specific stimuli and involving unique molecular players.
• These pathways are crucial for maintaining tissue homeostasis and responding to various physiological and pathological conditions.

Purpose of the Study:

• To review the molecular mechanisms of major regulated cell death pathways: apoptosis, necroptosis, pyroptosis, and ferroptosis.
• To discuss the individual and interconnected roles of these pathways in different cell types.
• To highlight their involvement in specific physiological and pathological functions.

Main Methods:

• Literature review of apoptosis, necroptosis, pyroptosis, and ferroptosis.
• Analysis of molecular activators and executioners for each pathway.
• Discussion of pathway interplay and cellular context.

Main Results:

• Apoptosis is mediated by caspase-3/7, activated by caspase-8 or -9.
• Necroptosis involves RIPK3 and MLKL, activated by cell death-inducing cytokines when caspase-8 is inhibited.
• Pyroptosis is induced by inflammatory caspases cleaving gasdermin D, while ferroptosis is an iron-dependent, caspase-independent necrotic death triggered by lipid peroxidation.

Conclusions:

• Regulated cell death pathways are diverse and execute distinct cellular functions.
• These pathways can act independently or interconnectively depending on the cellular context.
• Understanding these pathways is vital for comprehending physiological processes and developing therapeutics for diseases.