Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagy
Accumulation of Lewy bodies in dopaminergic neurons is associated to Parkinson disease (PD). The main component of Lewy bodies appears to be aggregates of alpha-synuclein (α-syn). Several mutations of the gene encoding this protein promote its aggregation. Thus, clustering of α-syn is considered a c...
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Taylor & Francis Group
2024-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2024.2314361 |
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| author | Rebeca Martín-Jiménez Olivier Lurette Etienne Hebert-Chatelain |
| author_facet | Rebeca Martín-Jiménez Olivier Lurette Etienne Hebert-Chatelain |
| author_sort | Rebeca Martín-Jiménez |
| collection | DOAJ |
| description | Accumulation of Lewy bodies in dopaminergic neurons is associated to Parkinson disease (PD). The main component of Lewy bodies appears to be aggregates of alpha-synuclein (α-syn). Several mutations of the gene encoding this protein promote its aggregation. Thus, clustering of α-syn is considered a central event in the onset of PD. An old theory also postulates that mitochondrial dysfunction represents another cause of PD pathogenesis. However, the impact of α-syn aggregates on mitochondria remains poorly understood considering the technical difficulties to discriminate between the different forms of α-syn. In this punctum, we describe our recent work in which we used a newly developed optogenetic tool to control the aggregation of α-syn and examine the impact on mitochondria. This work revealed that α-syn aggregates dynamically interact with mitochondria, triggering their depolarization and leading to cardiolipin translocation to the surface of mitochondria and mitophagy.Abbreviations: α-syn: alpha-synuclein; BNIP3L: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like; FUNDC1: FUN14 domain-containing protein 1; IMM: inner mitochondrial membrane; LIPA: light-induced protein aggregation; OMM: outer mitochondrial membrane; PD: Parkinson disease; SNc: substantia nigra par compacta; |
| format | Article |
| id | doaj-art-96e37761fef2496f8dfac422d08f0b6f |
| institution | OA Journals |
| issn | 2769-4127 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-96e37761fef2496f8dfac422d08f0b6f2025-08-20T02:30:42ZengTaylor & Francis GroupAutophagy Reports2769-41272024-12-013110.1080/27694127.2024.2314361Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagyRebeca Martín-Jiménez0Olivier Lurette1Etienne Hebert-Chatelain2Canada Research Chair in Mitochondrial Signaling and Physiopathology, Moncton, NB, CanadaCanada Research Chair in Mitochondrial Signaling and Physiopathology, Moncton, NB, CanadaCanada Research Chair in Mitochondrial Signaling and Physiopathology, Moncton, NB, CanadaAccumulation of Lewy bodies in dopaminergic neurons is associated to Parkinson disease (PD). The main component of Lewy bodies appears to be aggregates of alpha-synuclein (α-syn). Several mutations of the gene encoding this protein promote its aggregation. Thus, clustering of α-syn is considered a central event in the onset of PD. An old theory also postulates that mitochondrial dysfunction represents another cause of PD pathogenesis. However, the impact of α-syn aggregates on mitochondria remains poorly understood considering the technical difficulties to discriminate between the different forms of α-syn. In this punctum, we describe our recent work in which we used a newly developed optogenetic tool to control the aggregation of α-syn and examine the impact on mitochondria. This work revealed that α-syn aggregates dynamically interact with mitochondria, triggering their depolarization and leading to cardiolipin translocation to the surface of mitochondria and mitophagy.Abbreviations: α-syn: alpha-synuclein; BNIP3L: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like; FUNDC1: FUN14 domain-containing protein 1; IMM: inner mitochondrial membrane; LIPA: light-induced protein aggregation; OMM: outer mitochondrial membrane; PD: Parkinson disease; SNc: substantia nigra par compacta;https://www.tandfonline.com/doi/10.1080/27694127.2024.2314361Lewy bodiesmitochondrial membrane potentialmitochondrial fissionparkinson diseasePLSCR3selective autophagy |
| spellingShingle | Rebeca Martín-Jiménez Olivier Lurette Etienne Hebert-Chatelain Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagy Autophagy Reports Lewy bodies mitochondrial membrane potential mitochondrial fission parkinson disease PLSCR3 selective autophagy |
| title | Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagy |
| title_full | Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagy |
| title_fullStr | Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagy |
| title_full_unstemmed | Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagy |
| title_short | Alpha-synuclein aggregates trigger cardiolipin externalization and mitophagy |
| title_sort | alpha synuclein aggregates trigger cardiolipin externalization and mitophagy |
| topic | Lewy bodies mitochondrial membrane potential mitochondrial fission parkinson disease PLSCR3 selective autophagy |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2024.2314361 |
| work_keys_str_mv | AT rebecamartinjimenez alphasynucleinaggregatestriggercardiolipinexternalizationandmitophagy AT olivierlurette alphasynucleinaggregatestriggercardiolipinexternalizationandmitophagy AT etiennehebertchatelain alphasynucleinaggregatestriggercardiolipinexternalizationandmitophagy |