Considering Mitochondrial Dysfunction as a Contributing Cause of Intervertebral Disc Degeneration

Researchers here review the evidence for age-related loss of mitochondrial function to contribute to degenerative disc disease. It is certainly a contribution, but as for every aspect of aging it is very challenging to determine how important any given contribution is versus all of the others. So yes, mitochondrial quality control falters with age, and mitochondria become more damaged and dysfunctional as a result. This happens throughout the body. But is it more or less important for disc degeneration specifically than, say, the chronic inflammation of aging? Absent ways to individually fix each aspect of aging, so that results of treatment can be observed and compared directly, it is difficult to mount compelling arguments.

Intervertebral disc degeneration is the most common disease in chronic musculoskeletal diseases and the main cause of low back pain, which seriously endangers social health level and increases people's economic burden. Disc degeneration is characterized by nucleus pulposus (NP) cell apoptosis, extracellular matrix degradation, and disc structure changes. It progresses with age and under the influence of mechanical overload, oxidative stress, and genetics.

Mitochondria are not only the energy factories of cells, but also participate in a variety of cellular functions such as calcium homeostasis, regulation of cell proliferation, and control of apoptosis. The mitochondrial quality control system involves many mechanisms such as mitochondrial gene regulation, mitochondrial protein import, mitophagy, and mitochondrial dynamics. A large number of studies have confirmed that mitochondrial dysfunction is a key factor in the pathological mechanism of aging and intervertebral disc degeneration, and balancing mitochondrial quality control is extremely important for delaying and treating intervertebral disc degeneration.

In this paper, we first demonstrate the molecular mechanism of mitochondrial quality control in detail by describing mitochondrial biogenesis and mitophagy. Then, we describe the ways in which mitochondrial dysfunction leads to disc degeneration, and review in detail the current research on targeting mitochondria for the treatment of disc degeneration, hoping to draw inspiration from the current research to provide innovative perspectives for the treatment of disc degeneration.

Link: https://doi.org/10.1186/s12967-024-05943-9

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