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

Affiliation

Department of Spine Center, Zhongda Hospital, Medical School, Southeast University, China. Electronic address: [Email]

Abstract

OBJECTIVE : Bone marrow mesenchymal stem cells (BMSCs) show great potential in clinical applications such as in intervertebral disc degeneration. Nevertheless, environmental stress during the BMSC transplant or in the injured tissues is a catastrophic factor that causes cell toxicity and poor survival of BMSCs. Mitophagy plays a vital role in maintaining cellular homeostasis and defending against oxidative stress because this process could control mitochondrial quality and quantity by eliminating dysfunctional or damaged mitochondria that can cause cell death. However, the accurate mechanisms of mitophagy in protecting BMSCs against the harshness of oxidative stress remain largely unknown.
METHODS : BMSCs were treated with H2O2 for various time periods. Mitophagy response was evaluated through the expression levels of LC3-II, p62 and mitophagosomal formation by using Western blot and fluorescence analysis. Cell apoptosis was examined by flow cytometry and TUNEL assay. The interactions of mitophagy and apoptosis and the possible signalling pathways were investigated through the co-treatment of mitophagy inhibitor or mitophagy activator with H2O2.
RESULTS : Oxidative stress rapidly facilitated mitophagy through JNK at an early stage but decreased mitophagy and increased apoptosis at a late stage. Furthermore, mitophagy inhibition significantly enhanced the apoptosis in the cells treated by H2O2.
CONCLUSIONS : Induced mitophagy may play pivotal roles in protecting cells against oxidative stress in BMSCs.

Keywords

Apoptosis,Bone marrow mesenchymal stem cell,Mitophagy,Oxidative stress,Therapeutic strategy,

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