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

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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.

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

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  1. Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, 35392, Giessen, Germany

    Mehtap Civelek, Jan-Frederik Mehrkens, Nora-Maria Carstens, Elena Fitzenberger & Uwe Wenzel

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  1. Mehtap Civelek
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  2. Jan-Frederik Mehrkens
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Correspondence to Uwe Wenzel.

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Civelek, M., Mehrkens, JF., Carstens, NM. et al. Inhibition of mitophagy decreases survival of Caenorhabditis elegans by increasing protein aggregation. Mol Cell Biochem 452, 123–131 (2019). https://doi.org/10.1007/s11010-018-3418-5

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