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Molecular and Cellular Biochemistry

, Volume 452, Issue 1–2, pp 123–131 | Cite as

Inhibition of mitophagy decreases survival of Caenorhabditis elegans by increasing protein aggregation

  • Mehtap Civelek
  • Jan-Frederik Mehrkens
  • Nora-Maria Carstens
  • Elena Fitzenberger
  • Uwe WenzelEmail author
Article

Abstract

Autophagy of mitochondria, i.e., mitophagy, plays a crucial role in coping with stressors in the aging process, metabolic disturbances, and neurological disorders. Impairments of the process might consequently lead to enhanced accumulation of aged and aggregated proteins and reduced cellular integrity in response to stress. In the present study, we used the stress-sensitive mutant mev-1 of Caenorhabditis elegans to assess the effects of the knockdown of mitophagy relevant genes on survival under heat stress, the amount of autophagosomes, and on protein aggregation. RNA interference for dct-1, drp-1, eat-3, fis-1, fzo1, glb-1, pink-1, and pgam-5 all resulted in a significant reduction of survival time at 37 °C. These effects were associated with a decrease in autophagosomal flux of proteins, as indicated by increased accumulation of GFP-tagged SQST-1, and a reduced amount of lysosomes demonstrating that autophagy was hampered. Moreover, the gene knockdowns led to increased levels of reactive oxygen species in mitochondria and an enhanced protein aggregation. In conclusion, our studies show that mitophagy is of central importance to keep mitochondria functional in order to prevent production of excess reactive oxygen species and protein aggregation and finally a reduction of survival under heat stress.

Keywords

Mitochondria Protein aggregation Autophagy Proteostasis Reactive oxygen species Caenorhabditis elegans 

Notes

Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit organizations.

Compliance with ethical standards

Conflict of interest

All authors declare no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Interdisciplinary Research CenterJustus-Liebig-University of GiessenGiessenGermany

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