Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease
The maintenance of healthy mitochondria is essential for neuronal survival and relies upon mitochondrial quality control pathways involved in mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy (mitophagy). Mitochondrial dysfunction is critically implicated in Parkinson’s d...
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MDPI AG
2024-12-01
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| author | Lydia Shen Ulf Dettmer |
| author_facet | Lydia Shen Ulf Dettmer |
| author_sort | Lydia Shen |
| collection | DOAJ |
| description | The maintenance of healthy mitochondria is essential for neuronal survival and relies upon mitochondrial quality control pathways involved in mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy (mitophagy). Mitochondrial dysfunction is critically implicated in Parkinson’s disease (PD), a brain disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Consequently, impaired mitochondrial quality control may play a key role in PD pathology. This is affirmed by work indicating that genes such as PRKN and PINK1, which participate in multiple mitochondrial processes, harbor PD-associated mutations. Furthermore, mitochondrial complex-I-inhibiting toxins like MPTP and rotenone are known to cause Parkinson-like symptoms. At the heart of PD is alpha-synuclein (αS), a small synaptic protein that misfolds and aggregates to form the disease’s hallmark Lewy bodies. The specific mechanisms through which aggregated αS exerts its neurotoxicity are still unknown; however, given the vital role of both αS and mitochondria to PD, an understanding of how αS influences mitochondrial maintenance may be essential to elucidating PD pathogenesis and discovering future therapeutic targets. Here, the current knowledge of the relationship between αS and mitochondrial quality control pathways in PD is reviewed, highlighting recent findings regarding αS effects on mitochondrial biogenesis, dynamics, and autophagy. |
| format | Article |
| id | doaj-art-b493344ab86d4737bdfbb0b66ce49363 |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-b493344ab86d4737bdfbb0b66ce493632025-08-20T02:00:54ZengMDPI AGBiomolecules2218-273X2024-12-011412164910.3390/biom14121649Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s DiseaseLydia Shen0Ulf Dettmer1College of Arts & Sciences, Cornell University, Ithaca, NY 14853, USAAnn Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USAThe maintenance of healthy mitochondria is essential for neuronal survival and relies upon mitochondrial quality control pathways involved in mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy (mitophagy). Mitochondrial dysfunction is critically implicated in Parkinson’s disease (PD), a brain disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Consequently, impaired mitochondrial quality control may play a key role in PD pathology. This is affirmed by work indicating that genes such as PRKN and PINK1, which participate in multiple mitochondrial processes, harbor PD-associated mutations. Furthermore, mitochondrial complex-I-inhibiting toxins like MPTP and rotenone are known to cause Parkinson-like symptoms. At the heart of PD is alpha-synuclein (αS), a small synaptic protein that misfolds and aggregates to form the disease’s hallmark Lewy bodies. The specific mechanisms through which aggregated αS exerts its neurotoxicity are still unknown; however, given the vital role of both αS and mitochondria to PD, an understanding of how αS influences mitochondrial maintenance may be essential to elucidating PD pathogenesis and discovering future therapeutic targets. Here, the current knowledge of the relationship between αS and mitochondrial quality control pathways in PD is reviewed, highlighting recent findings regarding αS effects on mitochondrial biogenesis, dynamics, and autophagy.https://www.mdpi.com/2218-273X/14/12/1649α-synucleinParkinson’s diseasemitochondrial dysfunctionPINK1/ParkinPGC-1αmitochondrial fragmentation |
| spellingShingle | Lydia Shen Ulf Dettmer Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease Biomolecules α-synuclein Parkinson’s disease mitochondrial dysfunction PINK1/Parkin PGC-1α mitochondrial fragmentation |
| title | Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease |
| title_full | Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease |
| title_fullStr | Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease |
| title_full_unstemmed | Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease |
| title_short | Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease |
| title_sort | alpha synuclein effects on mitochondrial quality control in parkinson s disease |
| topic | α-synuclein Parkinson’s disease mitochondrial dysfunction PINK1/Parkin PGC-1α mitochondrial fragmentation |
| url | https://www.mdpi.com/2218-273X/14/12/1649 |
| work_keys_str_mv | AT lydiashen alphasynucleineffectsonmitochondrialqualitycontrolinparkinsonsdisease AT ulfdettmer alphasynucleineffectsonmitochondrialqualitycontrolinparkinsonsdisease |