Research on the molecular mechanism of intervertebral disc degeneration caused by mitochondrial dysfunction

Abstract

Intervertebral Disc Degeneration (IVDD) is the primary pathological basis of chronic low back pain, typically characterized by degeneration of the nucleus pulposus (NP), fissures in the annulus fibrosus (AF), and calcification of the cartilage endplates. These changes ultimately lead to nerve compression and loss of spinal function. Current treatment approaches are primarily symptomatic and cannot reverse disease progression. Therefore, a detailed understanding of the molecular mechanisms of IVDD and the exploration of targeted therapeutic strategies are of considerable clinical importance.Growing evidence indicates that mitochondrial dysfunction is a key factor in the pathogenesis of IVDD. Aberrations such as excessive production of reactive oxygen species (ROS), imbalance in mitochondrial dynamics, impaired mitophagy, and abnormal metabolic reprogramming converge to disrupt cellular activities, accelerate programmed cell death, and drive the breakdown of the extracellular matrix (ECM). This article comprehensively summarizes the role of mitochondrial damage in IVDD, with a focus on oxidative stress, dysregulated autophagy, and excessive mitochondrial fission. Furthermore, it evaluates emerging preclinical strategies aimed at restoring mitochondrial quality.From the perspective of bioenergetic dysfunction, this review proposes that interventions targeting the mitochondrial quality control network may establish a novel therapeutic paradigm for IVDD, thereby laying a theoretical foundation for translational and multidisciplinary research.