Abstract
Mitochondria are cytosolic organelles essential for cellular function and survival. The function of mitochondria is maintained by mitochondrial quality control systems including mitochondrial fission and fusion to adapt the altered environment and mitophagy for removal of damaged mitochondria. Mitochondrial dysfunction is closely involved in aging-related diseases. Intervertebral disc (IVD) degeneration, an aging-associated process, is the major contributor to low back pain. Growing evidence has suggested that the mitochondrial function in IVD cells is severely compromised during the degenerative process of IVD, and dysfunctional mitochondria along with impaired mitochondrial dynamics and mitophagy cause a series of cascade reactions that have been implicated in increased oxidative stress, senescence, matrix catabolism, and apoptosis of IVD cells, thereby contributing to the degeneration of IVD. Accordingly, therapies that target mitochondrial dysfunction and related mechanisms, such as ROS generation, mitophagy, and specific molecules and signaling, hold great promise. The present review summarizes the current state of the role of mitochondrial dysfunction in the pathophysiology of IVD degeneration and potential therapeutic strategies that could be developed.
Highlights
The intervertebral disc (IVD) is a fibrocartilaginous tissue interspacing and connecting adjacent vertebrae, which serves to absorb and transmit mechanical loading from the spine and permits movement of the spine [1]
Mitochondrial fusion is the combination of two mitochondria with the outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1 and MFN2) followed by Inner mitochondrial membrane (IMM) fusion, determined by optic atrophy 1 (OPA1) [34]
Exogenous ATP could significantly promote extracellular matrix (ECM) deposition and corresponding gene expression in nucleus pulposus (NP) cells and annulus fibrosus (AF) cells in three-dimensional agarose culture [85]. These findings indicate that normal metabolism of energy is essential for ECM homeostasis, while age-related disc cell mitochondrial and bioenergetic changes might contribute to the loss of matrix homeostasis that underlay disc degeneration
Summary
The intervertebral disc (IVD) is a fibrocartilaginous tissue interspacing and connecting adjacent vertebrae, which serves to absorb and transmit mechanical loading from the spine and permits movement of the spine [1]. NP cells act a critical role in producing extracellular matrix (ECM) components including type II collagen and proteoglycan, maintaining the integrity and homeostasis of IVD [3]. Mitochondria play a crucial role in energy production, mainly through the mechanism of oxidative phosphorylation [2]. These organelles contribute to key biochemical processes including the generation of reactive oxygen species (ROS) [11] and the regulation of calcium. Given its essential roles in cellular processes, it is not surprising that dysfunction or impairment of mitochondria will be implicated in a series of pathological processes, such as oxidative stress, senescence, apoptosis, and ECM degradation, causing detrimental effects on cell function and survival. The role of mitochondria in IVD degeneration is widely studied, and these studies have yielded a more comprehensive understanding of the pathophysiology of IVD degeneration and provided some promising therapeutic approaches for the treatment of IVD degeneration, which we aim to summarize and discuss in this review
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