AMBRA1-Mediated Mitophagy Counteracts Oxidative Stress and Apoptosis Induced by Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells

Frontiers in Cellular Neuroscience
Anthea Di RitaFrancesco Cecconi

Abstract

Therapeutic strategies are needed to protect dopaminergic neurons in Parkinson's disease (PD) patients. Oxidative stress caused by dopamine may play an important role in PD pathogenesis. Selective autophagy of mitochondria (mitophagy), mainly regulated by PINK1 and PARKIN, plays an important role in the maintenance of cell homeostasis. Mutations in those genes cause accumulation of damaged mitochondria, leading to nigral degeneration and early-onset PD. AMBRA1ActA is a fusion protein specifically expressed at the mitochondria, and whose expression has been shown to induce a powerful mitophagy in mammalian cells. Most importantly, the pro-autophagy factor AMBRA1 is sufficient to restore mitophagy in fibroblasts of PD patients carrying PINK1 and PARKIN mutations. In this study, we investigated the potential neuroprotective effect of AMBRA1-induced mitophagy against 6-hydroxydopamine (6-OHDA)- and rotenone-induced cell death in human neuroblastoma SH-SY5Y cells. We demonstrated that AMBRA1ActA overexpression was sufficient to induce mitochondrial clearance in SH-SY5Y cells. We found that apoptosis induced by 6-OHDA and rotenone was reversed by AMBRA1-induced mitophagy. Finally, transfection of SH-SY5Y cells with a vector encoding ...Continue Reading

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Citations

Mar 7, 2019·Reviews in the Neurosciences·Anthea Di Rita, Flavie Strappazzon
May 28, 2019·Cells·Monica Vara-PerezPatrizia Agostinis
Aug 23, 2019·Cell Death and Differentiation·Flavie StrappazzonFrancesco Cecconi
Sep 11, 2019·Nature Reviews. Neurology·Yujun HouVilhelm A Bohr
Apr 6, 2019·Nature Communications·Pasquale D'AcunzoFrancesco Cecconi
Oct 30, 2019·International Journal of Environmental Research and Public Health·Yu ZhangQi Zhang
Apr 16, 2020·Frontiers in Physiology·Flavia MessinaCarlo Rodolfo
Apr 28, 2020·Cell Death Discovery·Katharina BellPatricia Boya
Mar 17, 2019·Apoptosis : an International Journal on Programmed Cell Death·Hong JinBilei Wang
Jul 8, 2020·Antioxidants·Han-A Park, Amy C Ellis
Mar 28, 2019·Molecular Neurobiology·Livia La BarberaParaskevi Krashia
Sep 16, 2018·Nature Communications·Anthea Di RitaFrancesco Cecconi
Jan 29, 2019·Neural Regeneration Research·Ulfuara ShefaYoungbuhm Huh
Sep 22, 2018·Journal of Cell Science·Shani BialikAdi Kimchi
Jan 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xiao-Le WangYi Zhang
Apr 25, 2020·Mechanisms of Ageing and Development·Alfonso SchiaviNatascia Ventura
Feb 11, 2021·Cell Death Discovery·Katharina BellPatricia Boya
Jun 3, 2021·Antioxidants·Anna De GaetanoMarcello Pinti
Nov 21, 2021·Autophagy·Martina Di RienzoGian Maria Fimia
Dec 11, 2021·IUBMB Life·Jing Guo, Wei-Chung Chiang

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Methods Mentioned

BETA
transfection
confocal
Fluorescence
Assay
confocal microscopy
flow cytometry

Software Mentioned

GraphPad Prism
NIH ImageJ

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