LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy
Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to r...
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/537 |
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| author | Zulzikry Hafiz Abu Bakar Jean-Pierre Bellier Daijiro Yanagisawa Tomoko Kato Ken-ichi Mukaisho Ikuo Tooyama |
| author_facet | Zulzikry Hafiz Abu Bakar Jean-Pierre Bellier Daijiro Yanagisawa Tomoko Kato Ken-ichi Mukaisho Ikuo Tooyama |
| author_sort | Zulzikry Hafiz Abu Bakar |
| collection | DOAJ |
| description | Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal novel aspects of the pathology. Immunohistochemistry was used to assess the distribution and abnormal changes in FtMt and LC3 immunoreactivities. Colocalization analysis using double immunofluorescence was performed, and subcellular patterns were examined using 3D imaging and modeling. In the substantia nigra pars compacta (SNc), strong FtMt-IR and LC3-IR were observed in the neurons of PSP patients. In other midbrain regions, such as the superior colliculus, the FtMt-IR and LC3-IR remained unchanged. In the SNc, nigral neurons were categorized into four patterns based on subcellular LC3/FtMt immunofluorescence intensities, degree of colocalization, and subcellular overlapping. This categorization suggested that concomitant accumulation of LC3/FtMt is related to mitophagy processes. Using the LC3-IR to stage neuronal damage, we retraced LC3/FtMt patterns and revealed the progression of FtMt accumulation in nigral neurons. Informed by these findings, we proposed a hypothesis to explain the function of FtMt during PSP progression. |
| first_indexed | 2024-03-10T03:37:47Z |
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| id | doaj.art-92a5063b2c244f1ab76ca765a9ece574 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:37:47Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-92a5063b2c244f1ab76ca765a9ece5742023-11-23T11:41:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123153710.3390/ijms23010537LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear PalsyZulzikry Hafiz Abu Bakar0Jean-Pierre Bellier1Daijiro Yanagisawa2Tomoko Kato3Ken-ichi Mukaisho4Ikuo Tooyama5Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, JapanMolecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, JapanMolecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, JapanMolecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, JapanDepartment of Pathology of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, JapanMolecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, JapanMitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal novel aspects of the pathology. Immunohistochemistry was used to assess the distribution and abnormal changes in FtMt and LC3 immunoreactivities. Colocalization analysis using double immunofluorescence was performed, and subcellular patterns were examined using 3D imaging and modeling. In the substantia nigra pars compacta (SNc), strong FtMt-IR and LC3-IR were observed in the neurons of PSP patients. In other midbrain regions, such as the superior colliculus, the FtMt-IR and LC3-IR remained unchanged. In the SNc, nigral neurons were categorized into four patterns based on subcellular LC3/FtMt immunofluorescence intensities, degree of colocalization, and subcellular overlapping. This categorization suggested that concomitant accumulation of LC3/FtMt is related to mitophagy processes. Using the LC3-IR to stage neuronal damage, we retraced LC3/FtMt patterns and revealed the progression of FtMt accumulation in nigral neurons. Informed by these findings, we proposed a hypothesis to explain the function of FtMt during PSP progression.https://www.mdpi.com/1422-0067/23/1/537progressive supranuclear palsymitochondrial ferritinFtMtLC3mitophagymidbrain |
| spellingShingle | Zulzikry Hafiz Abu Bakar Jean-Pierre Bellier Daijiro Yanagisawa Tomoko Kato Ken-ichi Mukaisho Ikuo Tooyama LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy International Journal of Molecular Sciences progressive supranuclear palsy mitochondrial ferritin FtMt LC3 mitophagy midbrain |
| title | LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy |
| title_full | LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy |
| title_fullStr | LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy |
| title_full_unstemmed | LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy |
| title_short | LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy |
| title_sort | lc3 ftmt colocalization patterns reveal the progression of ftmt accumulation in nigral neurons of patients with progressive supranuclear palsy |
| topic | progressive supranuclear palsy mitochondrial ferritin FtMt LC3 mitophagy midbrain |
| url | https://www.mdpi.com/1422-0067/23/1/537 |
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