Optimizing mitochondrial maintenance in extended neuronal projections.
Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an i...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-06-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1009073 |
| _version_ | 1818931638327836672 |
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| author | Anamika Agrawal Elena F Koslover |
| author_facet | Anamika Agrawal Elena F Koslover |
| author_sort | Anamika Agrawal |
| collection | DOAJ |
| description | Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, a key aspect underlying many neurodegenerative disorders. |
| first_indexed | 2024-12-20T04:19:46Z |
| format | Article |
| id | doaj.art-caff8740e8fa484cb5bbe12f3ad495a6 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-20T04:19:46Z |
| publishDate | 2021-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-caff8740e8fa484cb5bbe12f3ad495a62022-12-21T19:53:40ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-06-01176e100907310.1371/journal.pcbi.1009073Optimizing mitochondrial maintenance in extended neuronal projections.Anamika AgrawalElena F KosloverNeurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, a key aspect underlying many neurodegenerative disorders.https://doi.org/10.1371/journal.pcbi.1009073 |
| spellingShingle | Anamika Agrawal Elena F Koslover Optimizing mitochondrial maintenance in extended neuronal projections. PLoS Computational Biology |
| title | Optimizing mitochondrial maintenance in extended neuronal projections. |
| title_full | Optimizing mitochondrial maintenance in extended neuronal projections. |
| title_fullStr | Optimizing mitochondrial maintenance in extended neuronal projections. |
| title_full_unstemmed | Optimizing mitochondrial maintenance in extended neuronal projections. |
| title_short | Optimizing mitochondrial maintenance in extended neuronal projections. |
| title_sort | optimizing mitochondrial maintenance in extended neuronal projections |
| url | https://doi.org/10.1371/journal.pcbi.1009073 |
| work_keys_str_mv | AT anamikaagrawal optimizingmitochondrialmaintenanceinextendedneuronalprojections AT elenafkoslover optimizingmitochondrialmaintenanceinextendedneuronalprojections |