Mitochondria-targeted therapy: a promising treatment strategy for intervertebral disc degeneration

Low back pain (LBP) is a prevalent musculoskeletal disorder worldwide, and intervertebral disc degeneration (IDD) constitutes its primary etiological factor. With the continuous advancement of research, an increasing number of studies have demonstrated that mitochondrial dysfunction is closely associated with IDD, and repairing damaged mitochondria represents a valuable target for intervening in IDD. Given the disadvantages of low efficacy and substantial side effects of conventional mitochondrial repair methods, it is urgent to establish efficient targeted repair strategies. This review discusses the role of mitochondrial dysfunction in the pathogenesis of IDD and the difficulties in repairing degenerated intervertebral discs (IVDs). Additionally, we review the physiological barriers and classification of mitochondria-targeted therapies (MTTs). In particular, we elaborate on the application of emerging MTTs strategies in IDD, including targeted small molecules, nano-drug delivery systems (NDDSs), and mitochondrial supplementation therapies. Furthermore, this review extensively explores the future challenges and directions of MTTs, aiming to provide a comprehensive framework for preclinical research and future clinical translation of MTTs.