Cargando…

Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease

Mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson’s disease (PD). Consistent with this concept, loss of function mutations in the serine/threonine kinase- PINK1 (PTEN-induced putative kinase-1) causes autosomal recessive early onset PD. While the functional role of...

Descripción completa

Detalles Bibliográficos
Autores principales: Soman, Smijin K., Dagda, Ruben K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593325/
https://www.ncbi.nlm.nih.gov/pubmed/34795558
http://dx.doi.org/10.3389/fnins.2021.769331
_version_ 1784599708957671424
author Soman, Smijin K.
Dagda, Ruben K.
author_facet Soman, Smijin K.
Dagda, Ruben K.
author_sort Soman, Smijin K.
collection PubMed
description Mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson’s disease (PD). Consistent with this concept, loss of function mutations in the serine/threonine kinase- PINK1 (PTEN-induced putative kinase-1) causes autosomal recessive early onset PD. While the functional role of f-PINK1 (full-length PINK1) in clearing dysfunctional mitochondria via mitophagy is extensively documented, our understanding of specific physiological roles that the non-mitochondrial pool of PINK1 imparts in neurons is more limited. PINK1 is proteolytically processed in the intermembrane space and matrix of the mitochondria into functional cleaved products (c-PINK1) that are exported to the cytosol. While it is clear that posttranslational processing of PINK1 depends on the mitochondria’s oxidative state and structural integrity, the functional roles of c-PINK1 in modulating neuronal functions are poorly understood. Here, we review the diverse roles played by c-PINK1 in modulating various neuronal functions. Specifically, we describe the non-canonical functional roles of PINK1, including but not limited to: governing mitochondrial movement, neuronal development, neuronal survival, and neurogenesis. We have published that c-PINK1 stimulates neuronal plasticity and differentiation via the PINK1-PKA-BDNF signaling cascade. In addition, we provide insight into how mitochondrial membrane potential-dependent processing of PINK1 confers conditional retrograde signaling functions to PINK1. Further studies delineating the role of c-PINK1 in neurons would increase our understanding regarding the role played by PINK1 in PD pathogenesis.
format Online
Article
Text
id pubmed-8593325
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85933252021-11-17 Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease Soman, Smijin K. Dagda, Ruben K. Front Neurosci Neuroscience Mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson’s disease (PD). Consistent with this concept, loss of function mutations in the serine/threonine kinase- PINK1 (PTEN-induced putative kinase-1) causes autosomal recessive early onset PD. While the functional role of f-PINK1 (full-length PINK1) in clearing dysfunctional mitochondria via mitophagy is extensively documented, our understanding of specific physiological roles that the non-mitochondrial pool of PINK1 imparts in neurons is more limited. PINK1 is proteolytically processed in the intermembrane space and matrix of the mitochondria into functional cleaved products (c-PINK1) that are exported to the cytosol. While it is clear that posttranslational processing of PINK1 depends on the mitochondria’s oxidative state and structural integrity, the functional roles of c-PINK1 in modulating neuronal functions are poorly understood. Here, we review the diverse roles played by c-PINK1 in modulating various neuronal functions. Specifically, we describe the non-canonical functional roles of PINK1, including but not limited to: governing mitochondrial movement, neuronal development, neuronal survival, and neurogenesis. We have published that c-PINK1 stimulates neuronal plasticity and differentiation via the PINK1-PKA-BDNF signaling cascade. In addition, we provide insight into how mitochondrial membrane potential-dependent processing of PINK1 confers conditional retrograde signaling functions to PINK1. Further studies delineating the role of c-PINK1 in neurons would increase our understanding regarding the role played by PINK1 in PD pathogenesis. Frontiers Media S.A. 2021-11-02 /pmc/articles/PMC8593325/ /pubmed/34795558 http://dx.doi.org/10.3389/fnins.2021.769331 Text en Copyright © 2021 Soman and Dagda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Soman, Smijin K.
Dagda, Ruben K.
Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease
title Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease
title_full Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease
title_fullStr Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease
title_full_unstemmed Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease
title_short Role of Cleaved PINK1 in Neuronal Development, Synaptogenesis, and Plasticity: Implications for Parkinson’s Disease
title_sort role of cleaved pink1 in neuronal development, synaptogenesis, and plasticity: implications for parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593325/
https://www.ncbi.nlm.nih.gov/pubmed/34795558
http://dx.doi.org/10.3389/fnins.2021.769331
work_keys_str_mv AT somansmijink roleofcleavedpink1inneuronaldevelopmentsynaptogenesisandplasticityimplicationsforparkinsonsdisease
AT dagdarubenk roleofcleavedpink1inneuronaldevelopmentsynaptogenesisandplasticityimplicationsforparkinsonsdisease