ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons
ABSTRACT Mitochondrial proteins are found in extracellular vesicles (EVs) such as neuron‐derived EVs (NEVs). Yet whether and how NEV‐borne mitochondrial proteins relate to the state of mitochondria in the parent neurons is unclear. Studying the mitochondrial ATP synthase in primary hippocampal neuro...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Journal of Extracellular Vesicles |
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| Online Access: | https://doi.org/10.1002/jev2.70140 |
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| author | Pamela J. Yao Carlos Nogueras‐Ortiz Krishna Ananthu Pucha Dimitrios Kapogiannis |
| author_facet | Pamela J. Yao Carlos Nogueras‐Ortiz Krishna Ananthu Pucha Dimitrios Kapogiannis |
| author_sort | Pamela J. Yao |
| collection | DOAJ |
| description | ABSTRACT Mitochondrial proteins are found in extracellular vesicles (EVs) such as neuron‐derived EVs (NEVs). Yet whether and how NEV‐borne mitochondrial proteins relate to the state of mitochondria in the parent neurons is unclear. Studying the mitochondrial ATP synthase in primary hippocampal neurons and their released EVs, we discovered that the abundance of ATP synthase in NEVs echoes the catalytic activity level of ATP synthase in neurons. We also observed, unexpectedly, that within the neuron, the quantity of ATP synthase remains constant irrespective of the level of its activity. Using non‐canonical amino acid tagging coupled with proximity ligation assay, we found that the amount of nascent ATP synthase is linearly correlated to its activity, which may contribute to maintaining the overall quantity of ATP synthase in the neuron stable. Furthermore, we identified a sub‐population of mitochondria‐derived vesicles (MDVs) that carry ATP synthase and are not targeted to lysosomal degradation. Our findings suggest a strategy used by neurons in regulating and fine‐tuning mitochondrial ATP synthase through MDV and NEV generation. Further studies are needed to elucidate the relationship between ATP synthase–containing‐NEVs and ‐MDVs. |
| format | Article |
| id | doaj-art-9dea4f16deb34fadb88206572250bda3 |
| institution | Kabale University |
| issn | 2001-3078 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-9dea4f16deb34fadb88206572250bda32025-08-26T07:24:44ZengWileyJournal of Extracellular Vesicles2001-30782025-08-01148n/an/a10.1002/jev2.70140ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent NeuronsPamela J. Yao0Carlos Nogueras‐Ortiz1Krishna Ananthu Pucha2Dimitrios Kapogiannis3Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program National Institutes of Health Baltimore Maryland USALaboratory of Clinical Investigation, National Institute on Aging Intramural Research Program National Institutes of Health Baltimore Maryland USALaboratory of Clinical Investigation, National Institute on Aging Intramural Research Program National Institutes of Health Baltimore Maryland USALaboratory of Clinical Investigation, National Institute on Aging Intramural Research Program National Institutes of Health Baltimore Maryland USAABSTRACT Mitochondrial proteins are found in extracellular vesicles (EVs) such as neuron‐derived EVs (NEVs). Yet whether and how NEV‐borne mitochondrial proteins relate to the state of mitochondria in the parent neurons is unclear. Studying the mitochondrial ATP synthase in primary hippocampal neurons and their released EVs, we discovered that the abundance of ATP synthase in NEVs echoes the catalytic activity level of ATP synthase in neurons. We also observed, unexpectedly, that within the neuron, the quantity of ATP synthase remains constant irrespective of the level of its activity. Using non‐canonical amino acid tagging coupled with proximity ligation assay, we found that the amount of nascent ATP synthase is linearly correlated to its activity, which may contribute to maintaining the overall quantity of ATP synthase in the neuron stable. Furthermore, we identified a sub‐population of mitochondria‐derived vesicles (MDVs) that carry ATP synthase and are not targeted to lysosomal degradation. Our findings suggest a strategy used by neurons in regulating and fine‐tuning mitochondrial ATP synthase through MDV and NEV generation. Further studies are needed to elucidate the relationship between ATP synthase–containing‐NEVs and ‐MDVs.https://doi.org/10.1002/jev2.70140ATP synthaseextracellular vesiclesmitochondriamitochondrial‐derived vesiclesmitovesiclesneurons |
| spellingShingle | Pamela J. Yao Carlos Nogueras‐Ortiz Krishna Ananthu Pucha Dimitrios Kapogiannis ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons Journal of Extracellular Vesicles ATP synthase extracellular vesicles mitochondria mitochondrial‐derived vesicles mitovesicles neurons |
| title | ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons |
| title_full | ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons |
| title_fullStr | ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons |
| title_full_unstemmed | ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons |
| title_short | ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons |
| title_sort | atp synthase abundance in neuronal extracellular vesicles reflects changes in the mitochondria of parent neurons |
| topic | ATP synthase extracellular vesicles mitochondria mitochondrial‐derived vesicles mitovesicles neurons |
| url | https://doi.org/10.1002/jev2.70140 |
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