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The Mitochondrial Routing of the Kv1.3 Channel

Voltage-gated potassium channels control neuronal excitability and cardiac action potentials. In addition, these proteins are involved in a myriad of cellular processes. The potassium channel Kv1.3 plays an essential role in the immune response mediated by leukocytes. Kv1.3 is functional both at the...

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Autores principales: Capera, Jesusa, Navarro-Pérez, María, Moen, Anne Stine, Szabó, Ildiko, Felipe, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990977/
https://www.ncbi.nlm.nih.gov/pubmed/35402277
http://dx.doi.org/10.3389/fonc.2022.865686
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author Capera, Jesusa
Navarro-Pérez, María
Moen, Anne Stine
Szabó, Ildiko
Felipe, Antonio
author_facet Capera, Jesusa
Navarro-Pérez, María
Moen, Anne Stine
Szabó, Ildiko
Felipe, Antonio
author_sort Capera, Jesusa
collection PubMed
description Voltage-gated potassium channels control neuronal excitability and cardiac action potentials. In addition, these proteins are involved in a myriad of cellular processes. The potassium channel Kv1.3 plays an essential role in the immune response mediated by leukocytes. Kv1.3 is functional both at the plasma membrane and the inner mitochondrial membrane. Plasma membrane Kv1.3 mediates cellular activation and proliferation, whereas mitochondrial Kv1.3 participates in cell survival and apoptosis. Therefore, this protein emerges as an important target in cancer therapies. Several forward-traffic motifs target the channel to the plasma membrane in a COPII-dependent manner. However, the mitochondrial import pathway for Kv1.3 is largely unknown. Here, we deciphered the mitochondrial routing of the mitoKv1.3 channel. Kv1.3 uses the TIM23 complex to translocate to the inner mitochondrial membrane. This mechanism is unconventional because the channel is a multimembrane spanning protein without a defined N-terminal presequence. We found that transmembrane domains cooperatively mediate Kv1.3 mitochondrial targeting and identified the cytosolic HSP70/HSP90 chaperone complex as a key regulator of the process. Our results provide insights into the mechanisms mediating the localization of Kv1.3 to mitochondrial membranes, further extending the knowledge of ion channel biogenesis and turnover in mitochondria.
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spelling pubmed-89909772022-04-09 The Mitochondrial Routing of the Kv1.3 Channel Capera, Jesusa Navarro-Pérez, María Moen, Anne Stine Szabó, Ildiko Felipe, Antonio Front Oncol Oncology Voltage-gated potassium channels control neuronal excitability and cardiac action potentials. In addition, these proteins are involved in a myriad of cellular processes. The potassium channel Kv1.3 plays an essential role in the immune response mediated by leukocytes. Kv1.3 is functional both at the plasma membrane and the inner mitochondrial membrane. Plasma membrane Kv1.3 mediates cellular activation and proliferation, whereas mitochondrial Kv1.3 participates in cell survival and apoptosis. Therefore, this protein emerges as an important target in cancer therapies. Several forward-traffic motifs target the channel to the plasma membrane in a COPII-dependent manner. However, the mitochondrial import pathway for Kv1.3 is largely unknown. Here, we deciphered the mitochondrial routing of the mitoKv1.3 channel. Kv1.3 uses the TIM23 complex to translocate to the inner mitochondrial membrane. This mechanism is unconventional because the channel is a multimembrane spanning protein without a defined N-terminal presequence. We found that transmembrane domains cooperatively mediate Kv1.3 mitochondrial targeting and identified the cytosolic HSP70/HSP90 chaperone complex as a key regulator of the process. Our results provide insights into the mechanisms mediating the localization of Kv1.3 to mitochondrial membranes, further extending the knowledge of ion channel biogenesis and turnover in mitochondria. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8990977/ /pubmed/35402277 http://dx.doi.org/10.3389/fonc.2022.865686 Text en Copyright © 2022 Capera, Navarro-Pérez, Moen, Szabó and Felipe https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Capera, Jesusa
Navarro-Pérez, María
Moen, Anne Stine
Szabó, Ildiko
Felipe, Antonio
The Mitochondrial Routing of the Kv1.3 Channel
title The Mitochondrial Routing of the Kv1.3 Channel
title_full The Mitochondrial Routing of the Kv1.3 Channel
title_fullStr The Mitochondrial Routing of the Kv1.3 Channel
title_full_unstemmed The Mitochondrial Routing of the Kv1.3 Channel
title_short The Mitochondrial Routing of the Kv1.3 Channel
title_sort mitochondrial routing of the kv1.3 channel
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990977/
https://www.ncbi.nlm.nih.gov/pubmed/35402277
http://dx.doi.org/10.3389/fonc.2022.865686
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