Coupling of mitochondrial state with active zone plasticity in early brain aging
Neurodegenerative diseases typically emerge after an extended prodromal period, underscoring the critical importance of initiating interventions during the early stages of brain aging to enhance later resilience. Changes in presynaptic active zone proteins (''PreScale'') are cons...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004324 |
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| author | Lu Fei Yongtian Liang Ulrich Kintscher Stephan J. Sigrist |
| author_facet | Lu Fei Yongtian Liang Ulrich Kintscher Stephan J. Sigrist |
| author_sort | Lu Fei |
| collection | DOAJ |
| description | Neurodegenerative diseases typically emerge after an extended prodromal period, underscoring the critical importance of initiating interventions during the early stages of brain aging to enhance later resilience. Changes in presynaptic active zone proteins (''PreScale'') are considered a dynamic, resilience-enhancing form of plasticity in the process of early, still reversible aging of the Drosophila brain. Aging, however, triggers significant changes not only of synapses but also mitochondria. While the two organelles are spaced in close proximity, likely reflecting a direct functional coupling in regard to ATP and Ca2+ homeostasis, the exact modes of coupling in the aging process remain to understood.We here show that genetic manipulations of mitochondrial functional status, which alters brain oxidative phosphorylation, ATP levels, or the production of reactive oxygen species (ROS), can bidirectionally regulate PreScale during early Drosophila brain aging. Conversely, genetic mimicry of PreScale resulted in decreased oxidative phosphorylation and ATP production, potentially due to reduced mitochondrial calcium (Ca2+) import.Our findings indicate the existence of a positive feedback loop where mitochondrial functional state and PreScale are reciprocally coupled to optimize protection during the early stages of brain aging. |
| format | Article |
| id | doaj-art-781240cde2d7450f8e3ab1a7508a82e2 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-781240cde2d7450f8e3ab1a7508a82e22025-01-14T04:12:07ZengElsevierRedox Biology2213-23172025-02-0179103454Coupling of mitochondrial state with active zone plasticity in early brain agingLu Fei0Yongtian Liang1Ulrich Kintscher2Stephan J. Sigrist3Institute for Biology/Genetics, Freie Universität Berlin, 14195, Berlin, GermanyInstitute for Biology/Genetics, Freie Universität Berlin, 14195, Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätmedizin Berlin, 10117, Berlin, GermanyInstitute of Pharmacology, Center for Cardiovascular Research, Charité Universitätmedizin Berlin, 10115, Berlin, Germany; German Centre for Cardiovascular Research (DZHK), partner site Berlin, 10117, Berlin, GermanyInstitute for Biology/Genetics, Freie Universität Berlin, 14195, Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätmedizin Berlin, 10117, Berlin, Germany; Corresponding author. Institute for Biology/Genetics, Freie Universität Berlin, 14195, Berlin, Germany.Neurodegenerative diseases typically emerge after an extended prodromal period, underscoring the critical importance of initiating interventions during the early stages of brain aging to enhance later resilience. Changes in presynaptic active zone proteins (''PreScale'') are considered a dynamic, resilience-enhancing form of plasticity in the process of early, still reversible aging of the Drosophila brain. Aging, however, triggers significant changes not only of synapses but also mitochondria. While the two organelles are spaced in close proximity, likely reflecting a direct functional coupling in regard to ATP and Ca2+ homeostasis, the exact modes of coupling in the aging process remain to understood.We here show that genetic manipulations of mitochondrial functional status, which alters brain oxidative phosphorylation, ATP levels, or the production of reactive oxygen species (ROS), can bidirectionally regulate PreScale during early Drosophila brain aging. Conversely, genetic mimicry of PreScale resulted in decreased oxidative phosphorylation and ATP production, potentially due to reduced mitochondrial calcium (Ca2+) import.Our findings indicate the existence of a positive feedback loop where mitochondrial functional state and PreScale are reciprocally coupled to optimize protection during the early stages of brain aging.http://www.sciencedirect.com/science/article/pii/S2213231724004324 |
| spellingShingle | Lu Fei Yongtian Liang Ulrich Kintscher Stephan J. Sigrist Coupling of mitochondrial state with active zone plasticity in early brain aging Redox Biology |
| title | Coupling of mitochondrial state with active zone plasticity in early brain aging |
| title_full | Coupling of mitochondrial state with active zone plasticity in early brain aging |
| title_fullStr | Coupling of mitochondrial state with active zone plasticity in early brain aging |
| title_full_unstemmed | Coupling of mitochondrial state with active zone plasticity in early brain aging |
| title_short | Coupling of mitochondrial state with active zone plasticity in early brain aging |
| title_sort | coupling of mitochondrial state with active zone plasticity in early brain aging |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004324 |
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