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The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity

Frison, M; Faccenda, D; Abeti, R; Rigon, M; Strobbe, D; England-Rendon, BS; Cash, D; Barnes, K; Sadeghian, M; Sajic, M; Wells, LA; Xia, D; Giunti, P; Smith, K; Mortiboys, H; Turkheimer, FE; Campanella, M

Authors

M Frison

D Faccenda

R Abeti

M Rigon

D Strobbe

BS England-Rendon

D Cash

K Barnes

M Sadeghian

M Sajic

LA Wells

D Xia

P Giunti

K Smith

H Mortiboys

FE Turkheimer

M Campanella



Abstract

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.

Citation

Frison, M., Faccenda, D., Abeti, R., Rigon, M., Strobbe, D., England-Rendon, B., …Campanella, M. (2021). The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity. Molecular Psychiatry, 26(7), 2721-2739. https://doi.org/10.1038/s41380-021-01050-z

Journal Article Type Article
Acceptance Date Feb 5, 2021
Publication Date 2021
Deposit Date Jan 6, 2022
Publicly Available Date Mar 29, 2024
Print ISSN 1359-4184
Publisher Springer Nature [academic journals on nature.com]
Peer Reviewed Peer Reviewed
Volume 26
Issue 7
Pages 2721-2739
DOI https://doi.org/10.1038/s41380-021-01050-z
Public URL https://rvc-repository.worktribe.com/output/1554575

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