Unraveling the pyroptosis-mitophagy axis: from molecular mechanisms to therapeutic opportunities
Year: 2026
Type: review
Abstract: Mitophagy and pyroptosis are central regulators of cell fate and inflammation, and they form a complex bidirectional network across many diseases. Mitophagy suppresses NLRP3 inflammasome activation by removing damaged mitochondria and thereby reducing mtROS and mtDNA release, which blocks pyroptosis. Conversely, pyroptosis can inhibit mitophagy by releasing inflammatory mediators and activating caspase-1, creating reinforcing or counterbalancing feedback loops. Signaling modules such as PINK1/Parkin, NOD2-RIPK2, Nrf2/HO-1, and AMPK critically modulate both mitophagy and pyroptosis. These processes interact broadly in organ injuries of the brain, liver, kidney, lung, bone, and heart to determine inflammation intensity and cell survival. Natural small molecules and traditional Chinese medicine that target the mitophagy-pyroptosis axis can modify pathological states including neurodegeneration, metabolic inflammation, and immune evasion, and thus represent a promising strategy for precision therapy.
Source: Frontiers in Immunology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G9001172781
OpenAlex ID: W7221607517