Immp2l gene knockout induces granulosa cell senescence by activation of cGAS-STING pathway via TFAM-mediated mtDNA leakage

Immp2l deficiency led to granulosa cell senescence characterized by a senescence-associated secretory phenotype (SASP).

• Granulosa cell senescence is associated with mitochondrial dysfunction and mitochondrial DNA leakage into the cytoplasm.
• The cytoplasmic mitochondrial DNA triggers the cGAS-STING pathway, leading to the activation of proinflammatory factors.
• Increased levels of Cyclophilin D40 and VDAC1 were observed in senescent granulosa cells, alongside elevated mitochondrial transcription factor A (TFAM).
• Knockdown of TFAM improved mitochondrial function and reduced cytoplasmic mitochondrial DNA, thereby inhibiting the cGAS-STING pathway.
• Treatment with procyanidin B2 decreased the SASP phenotype and senescence in granulosa cells by inhibiting the TFAM-mediated cGAS-STING pathway.

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