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Genetic Defects in Mitochondrial Dynamics in Caenorhabditis elegans Impact Ultraviolet C Radiation- and 6-hydroxydopamine-Induced Neurodegeneration.

Publication ,  Journal Article
Hartman, JH; Gonzalez-Hunt, C; Hall, SM; Ryde, IT; Caldwell, KA; Caldwell, GA; Meyer, JN
Published in: International journal of molecular sciences
June 2019

Parkinson's disease (PD) is one of the most common neurodegenerative disorders involving devastating loss of dopaminergic neurons in the substantia nigra. Early steps in PD pathogenesis include mitochondrial dysfunction, and mutations in mitochondrial genes have been linked to familial forms of the disease. However, low penetrance of mutations indicates a likely important role for environmental factors in PD risk through gene by environment interactions. Herein, we study how genetic deficiencies in mitochondrial dynamics processes including fission, fusion, and mitophagy interact with environmental exposures to impact neurodegeneration.We utilized the powerful model organism Caenorhabditis elegans to study ultraviolet C radiation (UVC)- and 6-hydroxydopamine-induced degeneration of fluorescently-tagged dopaminergic neurons in the background of fusion deficiency (MFN1/2 homolog, fzo-1), fission deficiency (DMN1L homolog, drp-1), and mitochondria-specific autophagy (mitophagy) deficiency (PINK1 and PRKN homologs, pink-1 and pdr-1).Overall, we found that deficiency in either mitochondrial fusion or fission sensitizes nematodes to UVC exposure (used to model common environmental pollutants) but protects from 6-hydroxydopamine-induced neurodegeneration. By contrast, mitophagy deficiency makes animals more sensitive to these stressors with an interesting exception-pink-1 deficiency conferred remarkable protection from 6-hydroxydopamine. We found that this protection could not be explained by compensatory antioxidant gene expression in pink-1 mutants or by differences in mitochondrial morphology.Together, our results support a strong role for gene by environment interactions in driving dopaminergic neurodegeneration and suggest that genetic deficiency in mitochondrial processes can have complex effects on neurodegeneration.

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Published In

International journal of molecular sciences

DOI

EISSN

1422-0067

ISSN

1422-0067

Publication Date

June 2019

Volume

20

Issue

13

Start / End Page

E3202

Related Subject Headings

  • Ultraviolet Rays
  • Ubiquitin-Protein Ligases
  • Radiation Tolerance
  • Protein Serine-Threonine Kinases
  • Parkinson Disease
  • Oxidopamine
  • Mitophagy
  • Mitochondrial Dynamics
  • GTP Phosphohydrolases
  • Dynamins
 

Citation

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Hartman, J. H., Gonzalez-Hunt, C., Hall, S. M., Ryde, I. T., Caldwell, K. A., Caldwell, G. A., & Meyer, J. N. (2019). Genetic Defects in Mitochondrial Dynamics in Caenorhabditis elegans Impact Ultraviolet C Radiation- and 6-hydroxydopamine-Induced Neurodegeneration. International Journal of Molecular Sciences, 20(13), E3202. https://doi.org/10.3390/ijms20133202
Hartman, Jessica H., Claudia Gonzalez-Hunt, Samantha M. Hall, Ian T. Ryde, Kim A. Caldwell, Guy A. Caldwell, and Joel N. Meyer. “Genetic Defects in Mitochondrial Dynamics in Caenorhabditis elegans Impact Ultraviolet C Radiation- and 6-hydroxydopamine-Induced Neurodegeneration.International Journal of Molecular Sciences 20, no. 13 (June 2019): E3202. https://doi.org/10.3390/ijms20133202.
Hartman JH, Gonzalez-Hunt C, Hall SM, Ryde IT, Caldwell KA, Caldwell GA, et al. Genetic Defects in Mitochondrial Dynamics in Caenorhabditis elegans Impact Ultraviolet C Radiation- and 6-hydroxydopamine-Induced Neurodegeneration. International journal of molecular sciences. 2019 Jun;20(13):E3202.
Hartman, Jessica H., et al. “Genetic Defects in Mitochondrial Dynamics in Caenorhabditis elegans Impact Ultraviolet C Radiation- and 6-hydroxydopamine-Induced Neurodegeneration.International Journal of Molecular Sciences, vol. 20, no. 13, June 2019, p. E3202. Epmc, doi:10.3390/ijms20133202.
Hartman JH, Gonzalez-Hunt C, Hall SM, Ryde IT, Caldwell KA, Caldwell GA, Meyer JN. Genetic Defects in Mitochondrial Dynamics in Caenorhabditis elegans Impact Ultraviolet C Radiation- and 6-hydroxydopamine-Induced Neurodegeneration. International journal of molecular sciences. 2019 Jun;20(13):E3202.

Published In

International journal of molecular sciences

DOI

EISSN

1422-0067

ISSN

1422-0067

Publication Date

June 2019

Volume

20

Issue

13

Start / End Page

E3202

Related Subject Headings

  • Ultraviolet Rays
  • Ubiquitin-Protein Ligases
  • Radiation Tolerance
  • Protein Serine-Threonine Kinases
  • Parkinson Disease
  • Oxidopamine
  • Mitophagy
  • Mitochondrial Dynamics
  • GTP Phosphohydrolases
  • Dynamins