Targeting mitophagy and ferroptosis: A new direction for the treatment of intervertebral disc degeneration.

One major cause of discomfort in the lower back pain (LBP) that significantly burdens both individuals and society is intervertebral disc degeneration (IVDD). The degenerative disease IVDD is typified by the death of nucleus pulposus cells (NPC) and the decomposition of extracellular matrix brought on by a number of factors. Current pharmacologic and surgical treatments are limited for the palliation and treatment of IVDD, and further exploration of the pathophysiologic mechanisms of IVDD is needed to provide new therapeutic strategies. In recent years, mitophagy, which maintains cell homeostasis, and ferroptosis, a newly discovered cell death mode, have been found to be closely related to IVDD. Importantly, these two processes do not operate in isolation; they interact dynamically through key signaling molecules such as reactive oxygen species (ROS) and pathways including AMPK/mTOR and Nrf2/Keap1, collectively influencing NPC survival and disc integrity. Therefore, we want to propose innovative ideas for IVDD treatment, utilizing the pertinent signaling axes and cytokines as entry sites, by examining the molecular mechanisms of ferroptosis and mitophagy.