Navigating the Web of Cell Death Through Oxidative Stress

Several cell death pathways are linked to oxidative stress, each with distinct mechanisms and roles in maintaining tissue homeostasis or driving the disease. These pathways include apoptosis, necrosis, ferroptosis, oxytosis, pyroptosis, and autophagy-related cell death. While all of these pathways can be triggered or modulated by oxidative stress, their molecular mechanisms, outcomes, and cellular signals differ.

Pathway	Trigger by Oxidative Stress	Key Features	Inflammatory Response	Mechanism
Apoptosis	DNA damage, ROS accumulation	Caspase activation, controlled cell death	Non-inflammatory	Intrinsic and extrinsic pathways via caspases
Necrosis	Overwhelming oxidative stress, trauma	Uncontrolled, cell swelling, rupture	Inflammatory	Unregulated, passive cell death
Ferroptosis	Iron-dependent lipid peroxidation	Iron, lipid peroxides, glutathione depletion	Non-inflammatory	GPX4 inhibition, lipid ROS damage
Oxytosis	Glutathione depletion, ROS in neurons	Neuron-specific, calcium dysregulation	Non-inflammatory	GSH depletion, ROS and calcium influx
Pyroptosis	ROS activating inflammasomes	Caspase-1, gasdermin D, inflammatory cytokines	Highly inflammatory	Inflammasome activation, cytokine release
Necroptosis	RIPK1/RIPK3 activation by ROS RIPK1/RIPK3 activation by ROS	RIPK3, MLKL, membrane rupture	Inflammatory	Regulated necrosis via RIPK1, RIPK3, MLKL
Autophagy-Related Death	Excessive autophagy, ROS	Autophagosome formation, survival mechanism	Non-inflammatory	Degradation of damaged organelles, excessive leads to death

References

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