Blocking the ETS1/DRP1 pathway may reduce disc degeneration by limiting excessive mitochondrial splitting

ETS1 is upregulated in severe intervertebral disc degeneration (IVDD) and is associated with increased mitochondrial fission.

• Nucleus pulposus cell (NPC) senescence and extracellular matrix (ECM) metabolic dysfunction are key features of IVDD.
• Inflammatory cytokines may induce ETS1 upregulation, which binds to the promoter of the gene encoding DRP1, activating its transcription.
• Increased levels of DRP1 could trigger excessive mitochondrial fission, leading to the accumulation of reactive oxygen species.
• This accumulation is linked to NPC senescence and degradation of the ECM.
• Targeting ETS1 or DRP1 may alleviate mitochondrial dysfunction and cellular senescence, potentially slowing IVDD progression.

Simplified