Absence of Gem1 (mammalian Miro/Rhot) mitigates alpha-synuclein toxicity in a yeast model of Parkinson's disease

Autor(es)

Melo, Thaiany Q. ; Palma, Flavio R. ; Gomes, Fernando ; Netto, Luis E. S. ; Ferrari, Merari F. R.

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Neuroscience; v. 122, p. 9-pg., 2022-09-01.

Resumo

Alpha-synuclein aggregation is a hallmark of Parkinson's disease (PD). Mutants A30P and A53T alpha-synuclein are known to exacerbate the toxicity of alpha-synuclein, which includes oxidative stress, mitochondrial and endoplasmic reticulum (ER) dysfunction. Saccharomyces cerevisiae (budding yeast) is a cellular model widely used to investigate mechanisms underlying neurodegenerative disorders, such as PD. In yeast, Gem1 (Miro/Rhot mammalian orthologue) coordinates mitochondrial dynamics and ER homeostasis, which is impaired in the presence of mutant alpha-synuclein and can lead to cell death. In this study, A30P or A53T alpha-synuclein were expressed in wild type or Delta Gem (deletion of Gem1 gene) yeast strains. Delta Gem cells presented decreased viability and increased mitochondrial H2O2 production and ER stress compared to wild type cells. However, in the presence of mutant alpha-synuclein, Delta Gem cells showed increased growth compared to cells that do not express mutant alpha-synuclein..Gem cells expressing A53T alpha-synuclein also presented reduced ER stress and increased ability to deal with oxidative stress. Together, our results suggest that deletion of Gem1 activates pathways that strengthen cells against other stressful agents such as the presence of mutant alpha-synuclein. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/06434-7 - Degradação da proteína tau hiperfosforilada e tráfego de organelas durante processos neurodegenerativos associados à agregação protéica em cultura de células do hipocampo
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/18961-2 - Estudo da autofagia como mecanismo para o desencadeamento de doenças neurodegenerativas
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07592-4 - Papel dos mecanismos de controle de qualidade na perda da proteostase em doenças neurodegenerativas dependentes da idade
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular