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Papers of the Week

Papers: 25 Nov 2023 - 1 Dec 2023

2023 Nov 23

Cell Signal



The role of endoplasmic reticulum stress, mitochondrial dysfunction and their crosstalk in intervertebral disc degeneration.


Yao D, Chen E, Li Y, Wang K, Liao Z, Li M, Huang L


Low back pain (LBP) is a pervasive global health issue. Roughly 40% of LBP cases are attributed to intervertebral disc degeneration (IVDD). While the underlying mechanisms of IVDD remain incompletely understood, it has been confirmed that apoptosis and extracellular matrix (ECM) degradation caused by many factors such as inflammation, oxidative stress, calcium (Ca) homeostasis imbalance leads to IVDD. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are involved in these processes. The initiation of ER stress precipitates cell apoptosis, and is also related to inflammation, levels of oxidative stress, and Ca homeostasis. Additionally, mitochondrial dynamics, antioxidative systems, disruption of Ca homeostasis are closely associated with Reactive Oxygen Species (ROS) and inflammation, promoting cell apoptosis. However, numerous crosstalk exists between the ER and mitochondria, where they interact through inflammatory cytokines, signaling pathways, ROS, or key molecules such as CHOP, forming positive and negative feedback loops. Furthermore, the contact sites between the ER and mitochondria, known as mitochondria-associated membranes (MAM), facilitate direct signal transduction such as Ca transfer. However, the current attention towards this issue is insufficient. Therefore, this review summarizes the impacts of ER stress and mitochondrial dysfunction on IVDD, along with the possibly potential crosstalk between them, aiming to unveil novel avenues for IVDD intervention.