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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...

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Autores principales: Davis, Kayla, Basu, Himanish, Izquierdo-Villalba, Ismael, Shurberg, Ethan, Schwarz, Thomas L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2022
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.
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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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