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2025 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 21, no 2, article id e1011554Article in journal (Refereed) Published
Abstract [en]
The Shaker/Kv1 subfamily of voltage-gated potassium (K+) channels is essential for modulating membrane excitability. Their loss results in prolonged depolarization and excessive calcium influx. These channels have also been implicated in a variety of other cellular processes, but the underlying mechanisms remain poorly understood. Through comprehensive screening of K+ channel mutants in C. elegans, we discovered that shk-1 mutants are highly susceptible to bacterial pathogen infection and oxidative stress. This vulnerability is associated with reduced glycogen levels and substantial mitochondrial dysfunction, including decreased ATP production and dysregulated mitochondrial membrane potential under stress conditions. SHK-1 is predominantly expressed and functions in body wall muscle to maintain glycogen storage and mitochondrial homeostasis. RNA-sequencing data reveal that shk-1 mutants have decreased expression of a set of cation-transporting ATPases (CATP), which are crucial for maintaining electrochemical gradients. Intriguingly, overexpressing catp-3, but not other catp genes, restores the depolarization of mitochondrial membrane potential under stress and enhances stress tolerance in shk-1 mutants. This finding suggests that increased catp-3 levels may help restore electrochemical gradients disrupted by shk-1 deficiency, thereby rescuing the phenotypes observed in shk-1 mutants. Overall, our findings highlight a critical role for SHK-1 in maintaining stress tolerance by regulating glycogen storage, mitochondrial homeostasis, and gene expression. They also provide insights into how Shaker/Kv1 channels participate in a broad range of cellular processes.
Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2025
National Category
Molecular Biology Infectious Medicine Cell Biology
Identifiers
urn:nbn:se:umu:diva-235380 (URN)10.1371/journal.pgen.1011554 (DOI)001415949000001 ()39913540 (PubMedID)2-s2.0-85217033990 (Scopus ID)
Funder
Swedish Research Council, 2021-06602Swedish Research Council, 2022-06725Swedish Research Council, 2024-00409Swedish Research Council, 2022- 00981Swedish Research Council, 2018-02216Swedish Research Council, 2024-04141Swedish Cancer Society, 23 3102 PjSwedish Cancer Society, 2023-2821The Kempe Foundations, SMK21-0024The Kempe Foundations, JCSMK24-0012EU, European Research Council, 802653 OXYGEN SENSING
2025-02-242025-02-242025-05-09Bibliographically approved