ABSTRACT SUBMISSION FORM
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TITLE*
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Autophagy in reduction of mutant ataxin-3 but not mitochondrial function are activatedby delivery of Pep-1-labeled mitochondriain Spinocerebellar Ataxia Type 3
AUTHOR(S)*
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Jui-Chih Chang1, Cheng-yi Yeh1, Ko-Hung Liu1, Bing-wen Soong2,3 and Chin-San Liu1,4
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1Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua 500, Taiwan
2Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan
3Department of Neurology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
4Department of Neurology, Changhua Christian Hospital, Changhua 500, Taiwan
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ABSTRACT*
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Mitochondrial dysfunction expedites the progression of spinocerebellar or sensory ataxiabut the central role is still undefined. Presently, mitochondrial regulation on pathologyof Spinocerebellar ataxia type 3 (SCA3) was studied bymitochondrial transplantation with Pep-1, a mitochondrial carrier 1. Allogeneic mitochondriaconjugated Pep-1 (P-Mito) or not were individually transplanted into cell neuroblastoma cells carried ATXN3 gene modified 78 CAG repeats (MJD78) and SCA3 transgenic mice (carried with an expanded 84 CAG repeat motif) (SCA3-84Q) mice with dramaticallyPurkinje cellsloss. We observed the decrease levels ofcytosolic soluble mutant ataxin-3and apoptosis suffering H2O2-induced oxidative stresseven without mitochondrial function recovery in treated MJD78 cells to compare with the non-treated control, which accompanied with the greater autophagy flux (a combination of increased LC3-II/LC3-I ratio and LC3-II levels and reduced p62/SQSTM1). The consistent finding was found in P-Mito-grafted SAC3-84Q mice with the rescue of motor coordinationexamined by rota-rod test and survival of cerebellar Purkinje cellsto compare with groups of sham-treated controls. Cerebellar graft of P-Mito not only restored efficiency of autophagosome/lysosome fusion revealed by LysoTracker staining but also promoted the localization of p62/SQSTM1 into lysosome shown by immunofluorescent double staining. Therefore, we prospects thatmitochondrial transplantation-activated autophagy may protect neurons from the toxic effects of a mutant polyglutamine protein, but the regulatory link which exists between graft mitochondrial and autophagy mechanism need further clarify.
Reference:
1 Liu, C. S., Chang, J. C., Kuo, S. J., Liu, K. H., Lin, T. T., Cheng, W. L., & Chuang, S. F. (2014). Delivering healthy mitochondria for the therapy of mitochondrial diseases and beyond.The international journal of biochemistry & cell biology,53, 141-146.
DEADLINE FOR ABSTRACT SUBMISSION：September30, 2018