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Oxidative stress impairs processive motility of the axonal transport motor KIF1A.

Overview

Authors: Adrien P Chen1,2, Himanshu Pandey1, William O Hancock1,2
ORCID iDs: Himanshu Pandey, William O Hancock
  1. Department of Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania, USA
  2. Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania, USA
Institutions: Pennsylvania State University (United States)
Journal: The Journal of biological chemistry, volume 302, issue 6, article 111471
Dates: received 17 December 2025; published online 17 April 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.jbc.2026.111471 · PMID 42001941 · PMCID PMC13196361 · OpenAlex W7154787740
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: cellular / molecular (subfield)
Methods: Evoked potentials
Keywords: kinesin, microtubule, oxidative stress, free radicals, neurodegenerative disease
MeSH: Axonal Transport*, Kinesins*, Oxidative Stress*, Animals, Hydrogen Peroxide (* major topic)
Topic: Microtubule and mitosis dynamics (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: The Pennsylvania State University; Foundation for the National Institutes of Health; NIGMS NIH HHS (R35 GM139568); National Institutes of Health (GM139568)
Citations: not cited yet (Europe PMC); 50 references in the paper
Research resources: RRID:SCR_024462

Abstract

The kinesin-3 family member, KIF1A is an essential motor protein that carries out intracellular transport in neurons. Previous work has established that: (1) intracellular transport can be impaired in neurodegenerative diseases such as Alzheimer's and Parkinson's; and (2) oxidative stress is elevated in neurodegenerative diseases and during aging. To date there has not been a systematic study of the effects of reactive oxygen species on kinesin motor proteins. We hypothesized that oxidative stress can damage kinesin, leading to decreased motility. To test our hypothesis, we treated KIF1A in vitro with varying concentrations of hydrogen peroxide (H2O2), a common reactive oxygen species, and characterized the impacts on KIF1A function. Pretreatment of KIF1A with H2O2 at concentrations of 1 mM and higher decreased motility in microtubule gliding assays. In single-molecule assays KIF1A was impacted in two ways: a fraction of motors moved with slowed velocity, while a fraction of motors moved only diffusively with no net directionality. Nonreducing SDS-PAGE of oxidized kinesin showed higher molecular weight bands, consistent with disulfide-bonded dimers and higher-order species. Treating oxidized motors with reducing agents reversed this cross-linking and partially restored motility. Replacing cysteine residues in the motor domain reduced the effects of moderate oxidation but did not prevent the severe degradation of motility at the highest H2O2 concentrations, indicating there is irreversible oxidative damage beyond only cysteine residues. Our results suggest that KIF1A can be impacted by oxidative stress and raise the possibility that oxidized KIF1A may be involved in the pathogenesis of neurodegenerative diseases.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Complete data for all figures are publicly available at: http://doi.org/10.26207/64f0-dq40.

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 5 keywords, 5 MeSH terms, 4 funders, 49 references, 1 RRID.

Cite

This paper

Chen, A. P., Pandey, H., & Hancock, W. O. (2026). Oxidative stress impairs processive motility of the axonal transport motor KIF1A. The Journal of biological chemistry, 302(6), 111471. https://doi.org/10.1016/j.jbc.2026.111471

BibTeX

@article{chen2026oxidative,
author = {Chen, Adrien P and Pandey, Himanshu and Hancock, William O},
title = {{Oxidative stress impairs processive motility of the axonal transport motor KIF1A}},
journal = {The Journal of biological chemistry},
year = {2026},
month = apr,
volume = {302},
number = {6},
pages = {111471},
publisher = {American Society for Biochemistry and Molecular Biology},
issn = {0021-9258},
doi = {10.1016/j.jbc.2026.111471},
url = {https://doi.org/10.1016/j.jbc.2026.111471},
pmid = {42001941},
pmcid = {PMC13196361}
}

RIS

TY - JOUR
AU - Chen, Adrien P
AU - Pandey, Himanshu
AU - Hancock, William O
TI - Oxidative stress impairs processive motility of the axonal transport motor KIF1A
T2 - The Journal of biological chemistry
J2 - J Biol Chem
PY - 2026
DA - 2026/04/17
VL - 302
IS - 6
SP - 111471
SN - 0021-9258
PB - American Society for Biochemistry and Molecular Biology
DO - 10.1016/j.jbc.2026.111471
UR - https://doi.org/10.1016/j.jbc.2026.111471
LA - en
ER -

CSL-JSON

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