GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury

GDF15 orchestrates sepsis tolerance through the SMAD7-HIF-1α axis, preserving mitochondrial integrity while resolving metabolic-inflammatory dysregulation, notably by suppressing the release of pro-inflammatory cytokines such as TNF-α and IL-6. This study identifies GDF15 as a central guardian of mitochondrial-immune homeostasis in sepsis, positioning it as both a robust severity biomarker and a promising therapeutic target for mitochondrial resuscitation.