Mitophagy is a protective response against oxidative damage in bone marrow mesenchymal stem cells

Fan, Ping; Xie, Xing-Hui; Chen, Changhong; Zhang, Po; Yang, Cheng; Peng, Xin; Wang, Yuntao

doi:10.1016/j.lfs.2019.05.027

Cited by 42 publications

(30 citation statements)

References 30 publications

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“…Autophagy and mitophagy might be also activated in a JNK-dependent manner [140,141]. JNK/MAPK pathway is initiated as a response to inflammation signals or oxidative stress [140,142].…”

Section: Non-canonical Pathwaymentioning

confidence: 99%

“…JNK/MAPK pathway is initiated as a response to inflammation signals or oxidative stress [140,142]. Wang et al reported a noncanonical and JNK-dependent mitophagy activation in bone marrow-derived mesenchymal stem cells, which is a common cell source for cartilage and IVD regeneration [141]. They found that oxidative stress induction for a limited period of time (< 1 h) activates mitophagy in a JNK-dependent manner.…”

Section: Non-canonical Pathwaymentioning

confidence: 99%

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Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

2021

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The prevalence of rheumatic and musculoskeletal diseases (RMDs) including osteoarthritis (OA) and low back pain (LBP) in aging societies present significant cost burdens to health and social care systems. Intervertebral disc (IVD) degeneration, which is characterized by disc dehydration, anatomical alterations, and extensive changes in extracellular matrix (ECM) composition, is an important contributor to LBP. IVD cell homeostasis can be disrupted by mitochondrial dysfunction. Mitochondria are the main source of energy supply in IVD cells and a major contributor to the production of reactive oxygen species (ROS). Therefore, mitochondria represent a double-edged sword in IVD cells. Mitochondrial dysfunction results in oxidative stress, cell death, and premature cell senescence, which are all implicated in IVD degeneration. Considering the importance of optimal mitochondrial function for the preservation of IVD cell homeostasis, extensive studies have been done in recent years to evaluate the efficacy of small molecules targeting mitochondrial dysfunction. In this article, we review the pathogenesis of mitochondrial dysfunction, aiming to highlight the role of small molecules and a selected number of biological growth factors that regulate mitochondrial function and maintain IVD cell homeostasis. Furthermore, molecules that target mitochondria and their mechanisms of action and potential for IVD regeneration are identified. Finally, we discuss mitophagy as a key mediator of many cellular events and the small molecules regulating its function.

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“…Autophagy and mitophagy might be also activated in a JNK-dependent manner [140,141]. JNK/MAPK pathway is initiated as a response to inflammation signals or oxidative stress [140,142].…”

Section: Non-canonical Pathwaymentioning

confidence: 99%

Section: Non-canonical Pathwaymentioning

confidence: 99%

Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

2021

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“…The results suggested that NPMSCs might initiate a self-protection mechanism to respond to oxidative damage at the early stage of H 2 O 2 treatment but failed at the late stage, which had been observed in many cell types. Fan et al [28] found that short-term oxidative stress could rapidly facilitate mitophagy to reduce oxidative damage in bone marrow-derived MSCs, and prolonged oxidative stress inhibited mitophagy and enhanced apoptosis. In endplate chondrocytes, results from Chen et al [29] also demonstrated that autophagy could be activated at the early stage of oxidative stress to protect against apoptosis, but prolonged oxidative stress decreased the autophagic flux.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1-Mediated Autophagy Protects against Oxidative Damage in Rat Nucleus Pulposus-Derived Mesenchymal Stem Cells

Chen

Liu

Zhao

et al. 2020

Oxidative Medicine and Cellular Longevity

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Although endogenous nucleus pulposus-derived mesenchymal stem cell- (NPMSC-) based regenerative medicine has provided promising repair strategy for intervertebral disc (IVD) degeneration, the hostile microenvironments in IVD, including oxidative stress, can negatively affect the survival and function of the NPMSCs and severely hinder the endogenous repair process. Therefore, it is of great importance to reveal the mechanisms of the endogenous repair failure caused by the adverse microenvironments in IVD. The aim of this study was to investigate the effect of oxidative stress on the rat NPMSCs and its underlying mechanism. Our results demonstrated that oxidative stress inhibited cell viability, induced apoptosis, and increased the production of reactive oxygen species (ROS) in NPMSCs. In addition, the results showed that the expression level of heme oxygenase-1 (HO-1) increased at an early stage but decreased at a late stage when NPMSCs were exposed to oxidative stress, and the oxidative damages of NPMSCs could be partially reversed by promoting the expression of HO-1. Further mechanistic analysis indicated that the protective effect of HO-1 against oxidative damage in NPMSCs was mediated by the activation of autophagy. Taken together, our study revealed that oxidative stress could inhibit cell viability, induce apoptosis, and increase ROS production in NPMSCs, and HO-1-mediated autophagy might act as a protective response to the oxidative damage. These findings might enhance our understanding on the mechanism of the endogenous repair failure during IVD degeneration and provide novel research direction for the endogenous repair of IVD degeneration.

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“…Dysfunctional mitochondria are selectively degraded in a process termed "mitophagy" to maintain mitochondrial homeostasis. Activation of mitophagy in BMSCs occurs at an early stage of reactive oxygen species (ROS) stress through Jun N-terminal kinase (JNK) pathway, but declines at a late stage of ROS stress [18]. Phosphatase and tensin homolog-(PTEN-) induced kinase 1 (PINK1)/Parkin pathway, which is normally involved in the clearance of dysfunctional mitochondria [19,20], is also required for infused MSCs to restore mitophagy pathways in hyperglycemia-challenged endothelial cells [21].…”

Section: Mitochondrial Transfer Impacts Cellularmentioning

confidence: 99%

“…Mitochondria play a critical role in cellular apoptosis [ 28 ]. ROS, a major product of mitochondria metabolism, in turn exerts a significant impact on mitochondria and mitochondria-mediated apoptosis [ 18 ]. Normally, the first stage of apoptosis involves elevated mitochondrial membrane permeability, which allows apoptogenic factors such as Bcl-2 to pass through OMM and to interrupt the electrochemical gradient in IMM.…”

Section: Mitochondrial Transfer Impacts Cellular Metabolism and Inmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cell-Mediated Mitochondrial Transfer and the Therapeutic Potential in Treatment of Neurological Diseases

Han

Zheng

Wang

et al. 2020

Stem Cells International

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Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells that can be derived from various tissues. Due to their regenerative and immunomodulatory properties, MSCs have been extensively researched and tested for treatment of different diseases/indications. One mechanism that MSCs exert functions is through the transfer of mitochondria, a key player involved in many biological processes in health and disease. Mitochondria transfer is bidirectional and has an impact on both donor and recipient cells. In this review, we discussed how MSC-mediated mitochondrial transfer may affect cellular metabolism, survival, proliferation, and differentiation; how this process influences inflammatory processes; and what is the molecular machinery that mediates mitochondrial transfer. In the end, we summarized recent advances in preclinical research and clinical trials for the treatment of stroke and spinal cord injury, through application of MSCs and/or MSC-derived mitochondria.

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Mitophagy is a protective response against oxidative damage in bone marrow mesenchymal stem cells

Cited by 42 publications

References 30 publications

Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration

Heme Oxygenase-1-Mediated Autophagy Protects against Oxidative Damage in Rat Nucleus Pulposus-Derived Mesenchymal Stem Cells

Mesenchymal Stem/Stromal Cell-Mediated Mitochondrial Transfer and the Therapeutic Potential in Treatment of Neurological Diseases

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