MitoQ protects dopaminergic neurons in a 6-OHDA induced PD model by enhancing Mfn2-dependent mitochondrial fusion via activation of PGC-1α.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Ye XiGang Zhao

Abstract

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra compacta (SNc). Although mitochondrial dysfunction is the critical factor in the pathogenesis of PD, the underlying molecular mechanisms are not well understood, and as a result, effective medical interventions are lacking. Mitochondrial fission and fusion play important roles in the maintenance of mitochondrial function and cell viability. Here, we investigated the effects of MitoQ, a mitochondria-targeted antioxidant, in 6-hydroxydopamine (6-OHDA)-induced in vitro and in vivo PD models. We observed that 6-OHDA enhanced mitochondrial fission by decreasing the expression of Mfn1, Mfn2 and OPA1 as well as by increasing the expression of Drp1 in the dopaminergic (DA) cell line SN4741. Notably, MitoQ treatment particularly upregulated the Mfn2 protein and mRNA levels and promoted mitochondrial fusion in the presence of 6-OHDA in a Mfn2-dependent manner. In addition, MitoQ also stabilized mitochondrial morphology and function in the presence of 6-OHDA, which further suppressed the formation of reactive oxygen species (ROS), as well as ameliorated mitochondrial fragmentation and cellular apoptosis. Moreover, the activation o...Continue Reading

Citations

Feb 20, 2019·Frontiers in Neuroscience·Xiu-Yun ZhaoQuan-Hong Ma
Aug 15, 2019·Neurochemical Research·Qi ZhangHao Meng
May 8, 2020·Oxidative Medicine and Cellular Longevity·Monika PichlaIzabela Sadowska-Bartosz
May 30, 2020·International Journal of Molecular Sciences·Serena StangaAlessandro Vercelli
Sep 11, 2020·Neural Plasticity·Baoyi FengHao Wu
Aug 21, 2020·Critical Reviews in Food Science and Nutrition·Jing YangJiajia Song
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Jul 14, 2020·Frontiers in Cellular Neuroscience·Xu YanXinwen Zhang
Feb 1, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Seulhee KimLufang Zhou
Oct 20, 2020·Journal of Parkinson's Disease·Max BorscheAnne Grünewald
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Jan 16, 2021·European Journal of Pharmacology·Bhupesh VaidyaShyam Sunder Sharma
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