Mitochondrial Dysfunction in Oxidative Stress‐Mediated Intervertebral Disc Degeneration

Abstract

Intervertebral disc degeneration (IVDD) is the most common contributor to low back pain (LBP). Recent studies have found that oxidative stress and reactive oxygen species (ROS) play an important role in IVDD. As a by‐product of aerobic respiration, ROS is mainly produced in the mitochondria by the electron transport chain and other mitochondrial located proteins. With the excessive accumulation of ROS, mitochondria are also the primary target of ROS attack in disc cells. A disrupted balance between intracellular ROS production and antioxidant capacity will lead to oxidative stress, which is the key contributor to cell apoptosis, cell senescence, excessive autophagy, and mitochondrial dysfunction. As the pivotal ingredient of oxidative stress, mitochondrial dysfunction manifests as imbalanced mitochondrial dynamics and dysregulated mitophagy. Mitochondria can alter their own dynamics through the process of fusion and fission, so that disabled mitochondria can be separated from the mitochondrial pool. Moreover, mitophagy participates by clearing these dysfunctional mitochondria. Abnormality in any of these processes either increases the production or decreases the clearance of ROS, leading to a vicious cycle that results in the death of intervertebral disc cells in large quantities, combined with degradation of the extracellular matrix and overproduction of matrix metalloproteinase. In this review, we explain the changes in mitochondrial morphology and function during oxidative stress‐mediated IVDD and highlight the important role of mitochondria in this process. Eventually, we summarize the IVDD therapeutic strategies targeting mitochondrial dysfunction based on current understanding of the role of oxidative stress in IVDD.

Senescent response in inner annulus fibrosus cells in response to TNFα, H2O2, and TNFα-induced nucleus pulposus senescent secretome

“…Although H 2 O 2 accumulation within the disc is well characterized (25,(39)(40)(41), to our knowledge this is the first study to demonstrate that H 2 O 2 , and not the cytokine TNFα, may be a principle driver of senescence in the iAF and importantly, that it may act as a signaling molecule between the NP and iAF. H 2 O 2 can be transported across the plasma membrane through aquaporins, which are known to be expressed by both NP and AF cells (42,43), and has been proposed to facilitate cell-to-cell signaling (44).…”

“…NOX2 and 4 expression has been shown to increase within the IVD during degeneration in rats (22), and in NP cells following exposure to IL1 or ROS in-vitro (23,24). Mitochondrial dysfunction has also been associated with IVD degeneration and has been proposed to contribute to ROS-induced damage within the tissues of the IVD (25). In response to oxidative stress, mammalian cells have four enzymes that compose the primary ROS response: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) (26), and peroxiredoxins (PRX).…”

Proteomic Profiling Reveals Increased Glycolysis, Decreased Oxidoreductase Activity and Fatty Acid Degradation in Skin Derived Fibroblasts from LHON Patients Bearing m.G11778A

“…Tun A. et al performed mitochondrial proteomic analysis using skin fibroblasts from LHON patients with the m.G11778A mutation and found that bioenergetic derangements and poor protein quality control systems lead to different penetrance [ 17 ]. The mitochondrion is an important organelle that regulates various cellular activities [ 18 , 19 , 20 ]. Mitochondrial dysfunction caused by genetic variation may lead to a variety of function disorders and even changes in protein expression profile, which may also contribute to heterogeneity.…”

Efeito da doença degenerativa dos discos intervertebrais na função do sistema estomatognático de indivíduos adultos

“…A segunda hipótese alternativa assegurou que o grupo com degeneração dos discos intervertebrais apresentou menor pressão dos tecidos orofaciais como da língua e dos músculos bucinador e orbicular da boca. Essa hipótese foi baseada no pressuposto que a doença degenerativa dos discos intervertebrais tem como patogênese também a disfunção mitocondrial que proporciona aumento do estresse oxidativo, apoptose e catabolismo das células do disco que desencadearia menor força dos tecidos do corpo humano como por exemplo o muscular (WANG et al, 2022).…”

“…Segundo estudos anteriores, um equilíbrio interrompido entre a produção excessivo de níveis de espécies reativas de oxigênio intracelular e a capacidade antioxidante pode levar ao estresse oxidativo, sendo o principal contribuinte para a apoptose celular, autofagia excessiva e disfunção mitocondrial (WANG et al, 2022;ZHANG et al, 2022). Fibras musculares danificadas são consideradas também consequências de reações de origem sistêmicas, como reações em relação a disfunção mitocondrial que proporciona redução na produção de força muscular (LEDUC-GAUDET et al, 2021) YAGI et al, 2017).…”