TY - JOUR
T1 - The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity
AU - Frison, Michele
AU - Faccenda, Danilo
AU - Abeti, Rosella
AU - Rigon, Manuel
AU - Strobbe, Daniela
AU - England-Rendon, Britannie S.
AU - Cash, Diana
AU - Barnes, Katy
AU - Sadeghian, Mona
AU - Sajic, Marija
AU - Wells, Lisa A.
AU - Xia, Dong
AU - Giunti, Paola
AU - Smith, Kenneth
AU - Mortiboys, Heather
AU - Turkheimer, Federico E.
AU - Campanella, Michelangelo
N1 - © 2021, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
PY - 2021/7/31
Y1 - 2021/7/31
N2 - Dysfunctional mitochondria characterise Parkinson's Disease (PD). Uncovering etiological molecules, which harm the homeostasis of mitochondria in response to pathological cues, is therefore pivotal to inform early diagnosis and therapy in the condition, especially in its idiopathic forms. This study proposes the 18 kDa Translocator Protein (TSPO) to be one of those. Both in vitro and in vivo data show that neurotoxins, which phenotypically mimic PD, increase TSPO to enhance cellular redox-stress, susceptibility to dopamine-induced cell death, and repression of ubiquitin-dependent mitophagy. TSPO amplifies the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signalling, forming positive feedback, which represses the transcription factor EB (TFEB) and the controlled production of lysosomes. Finally, genetic variances in the transcriptome confirm that TSPO is required to alter the autophagy-lysosomal pathway during neurotoxicity.
AB - Dysfunctional mitochondria characterise Parkinson's Disease (PD). Uncovering etiological molecules, which harm the homeostasis of mitochondria in response to pathological cues, is therefore pivotal to inform early diagnosis and therapy in the condition, especially in its idiopathic forms. This study proposes the 18 kDa Translocator Protein (TSPO) to be one of those. Both in vitro and in vivo data show that neurotoxins, which phenotypically mimic PD, increase TSPO to enhance cellular redox-stress, susceptibility to dopamine-induced cell death, and repression of ubiquitin-dependent mitophagy. TSPO amplifies the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signalling, forming positive feedback, which represses the transcription factor EB (TFEB) and the controlled production of lysosomes. Finally, genetic variances in the transcriptome confirm that TSPO is required to alter the autophagy-lysosomal pathway during neurotoxicity.
UR - https://www.scopus.com/pages/publications/85116650282
U2 - 10.1038/s41380-021-01050-z
DO - 10.1038/s41380-021-01050-z
M3 - Article
C2 - 33664474
AN - SCOPUS:85116650282
SN - 1359-4184
VL - 26
SP - 2721
EP - 2739
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -