Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies
In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as...
| Published in: | Biomedicines |
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| Main Authors: | , |
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/4/376 |
| _version_ | 1850094172820733952 |
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| author | Chantal B. Lucini Ralf J. Braun |
| author_facet | Chantal B. Lucini Ralf J. Braun |
| author_sort | Chantal B. Lucini |
| collection | DOAJ |
| container_title | Biomedicines |
| description | In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research. |
| format | Article |
| id | doaj-art-e0724e341c1941d7bc4f28e97fadfdb1 |
| institution | Directory of Open Access Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-e0724e341c1941d7bc4f28e97fadfdb12025-08-20T00:07:40ZengMDPI AGBiomedicines2227-90592021-04-019437610.3390/biomedicines9040376Mitochondrion-Dependent Cell Death in TDP-43 ProteinopathiesChantal B. Lucini0Ralf J. Braun1Research Area Neurodegenerative Diseases, Center for Biosciences, Faculty of Medicine/Dental Medicine, Danube Private University, 3500 Krems an der Donau, AustriaResearch Area Neurodegenerative Diseases, Center for Biosciences, Faculty of Medicine/Dental Medicine, Danube Private University, 3500 Krems an der Donau, AustriaIn the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.https://www.mdpi.com/2227-9059/9/4/376TDP-43proteinopathymitochondriamitochondrial permeabilizationmtDNAapoptosis |
| spellingShingle | Chantal B. Lucini Ralf J. Braun Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies TDP-43 proteinopathy mitochondria mitochondrial permeabilization mtDNA apoptosis |
| title | Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies |
| title_full | Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies |
| title_fullStr | Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies |
| title_full_unstemmed | Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies |
| title_short | Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies |
| title_sort | mitochondrion dependent cell death in tdp 43 proteinopathies |
| topic | TDP-43 proteinopathy mitochondria mitochondrial permeabilization mtDNA apoptosis |
| url | https://www.mdpi.com/2227-9059/9/4/376 |
| work_keys_str_mv | AT chantalblucini mitochondriondependentcelldeathintdp43proteinopathies AT ralfjbraun mitochondriondependentcelldeathintdp43proteinopathies |