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Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex
Mitochondrial transport relies on a motor–adaptor complex containing Miro1, a mitochondrial outer membrane protein with two GTPase domains, and TRAK1/2, kinesin-1, and dynein. Using a peroxisome-directed Miro1, we quantified the ability of GTPase mutations to influence the peroxisomal recruitment of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615026/ https://www.ncbi.nlm.nih.gov/pubmed/36302649 http://dx.doi.org/10.26508/lsa.202201406 |
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author | Davis, Kayla Basu, Himanish Izquierdo-Villalba, Ismael Shurberg, Ethan Schwarz, Thomas L |
author_facet | Davis, Kayla Basu, Himanish Izquierdo-Villalba, Ismael Shurberg, Ethan Schwarz, Thomas L |
author_sort | Davis, Kayla |
collection | PubMed |
description | Mitochondrial transport relies on a motor–adaptor complex containing Miro1, a mitochondrial outer membrane protein with two GTPase domains, and TRAK1/2, kinesin-1, and dynein. Using a peroxisome-directed Miro1, we quantified the ability of GTPase mutations to influence the peroxisomal recruitment of complex components. Miro1 whose N-GTPase is locked in the GDP state does not recruit TRAK1/2, kinesin, or P135 to peroxisomes, whereas the GTP state does. Similarly, the expression of the MiroGAP VopE dislodges TRAK1 from mitochondria. Miro1 C-GTPase mutations have little influence on complex recruitment. Although Miro2 is thought to support mitochondrial motility, peroxisome-directed Miro2 did not recruit the other complex components regardless of the state of its GTPase domains. Neurons expressing peroxisomal Miro1 with the GTP-state form of the N-GTPase had markedly increased peroxisomal transport to growth cones, whereas the GDP-state caused their retention in the soma. Thus, the N-GTPase domain of Miro1 is critical for regulating Miro1’s interaction with the other components of the motor–adaptor complex and thereby for regulating mitochondrial motility. |
format | Online Article Text |
id | pubmed-9615026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-96150262022-10-29 Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex Davis, Kayla Basu, Himanish Izquierdo-Villalba, Ismael Shurberg, Ethan Schwarz, Thomas L Life Sci Alliance Research Articles Mitochondrial transport relies on a motor–adaptor complex containing Miro1, a mitochondrial outer membrane protein with two GTPase domains, and TRAK1/2, kinesin-1, and dynein. Using a peroxisome-directed Miro1, we quantified the ability of GTPase mutations to influence the peroxisomal recruitment of complex components. Miro1 whose N-GTPase is locked in the GDP state does not recruit TRAK1/2, kinesin, or P135 to peroxisomes, whereas the GTP state does. Similarly, the expression of the MiroGAP VopE dislodges TRAK1 from mitochondria. Miro1 C-GTPase mutations have little influence on complex recruitment. Although Miro2 is thought to support mitochondrial motility, peroxisome-directed Miro2 did not recruit the other complex components regardless of the state of its GTPase domains. Neurons expressing peroxisomal Miro1 with the GTP-state form of the N-GTPase had markedly increased peroxisomal transport to growth cones, whereas the GDP-state caused their retention in the soma. Thus, the N-GTPase domain of Miro1 is critical for regulating Miro1’s interaction with the other components of the motor–adaptor complex and thereby for regulating mitochondrial motility. Life Science Alliance LLC 2022-10-27 /pmc/articles/PMC9615026/ /pubmed/36302649 http://dx.doi.org/10.26508/lsa.202201406 Text en © 2022 Davis et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Davis, Kayla Basu, Himanish Izquierdo-Villalba, Ismael Shurberg, Ethan Schwarz, Thomas L Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex |
title | Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex |
title_full | Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex |
title_fullStr | Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex |
title_full_unstemmed | Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex |
title_short | Miro GTPase domains regulate the assembly of the mitochondrial motor–adaptor complex |
title_sort | miro gtpase domains regulate the assembly of the mitochondrial motor–adaptor complex |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615026/ https://www.ncbi.nlm.nih.gov/pubmed/36302649 http://dx.doi.org/10.26508/lsa.202201406 |
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