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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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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 |
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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 |
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