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Effects of miro-1 silencing upon mitophagy and neuronal death during alpha-synuclein overexpression

Grant number: 18/12978-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2018
Effective date (End): September 30, 2019
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Merari de Fátima Ramires Ferrari
Grantee:Eduardo Oliveira de Queiroz
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The presence of non-functional mitochondria in neurons signals to cellular death. With the assistance of specific motor proteins such as Miro-1 the mitochondria are recycled constantly. However Miro-1 may not be exclusively associated with mitochondria traffic, but also with the cytoskeleton, endoplasmic reticulum and calcium homeostasis. Recent results from our laboratory point that the absence of Miro in yeasts protects these cells from toxicity promoted by overexpression of alfa-synuclein (protein associated with Parkinson's disease and other synucleinopathies). Therefore, this study aims to analyze the effects of knockdown of Miro-1 through CRISPR/Cas9 in neurons derived from neuroblatoma cells that express wildtype and mutant alfa synuclein (A30P and A53T) regarding cell death and mitophagy.