Issue 7, 2025

An environmentally relevant concentration of 6-PPD quinone inhibits two types of mitophagy to cause mitochondrial dysfunction and lifespan reduction in Caenorhabditis elegans

Abstract

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6-PPDQ) is widely distributed in the environment and bioavailable to organisms. Exposure to 6-PPDQ can impair the mitochondrial function. However, the underlying mechanisms for 6-PPDQ-induced mitochondrial dysfunction remain largely unclear. Mitophagy is important for organisms to maintain normal mitochondrial function. In the current study, Caenorhabditis elegans was employed as model to determine the role of mitophagy suppression in 6-PPDQ-induced toxicity. After exposure to 6-PPDQ, it was found that, although mitophagy was increased by 0.1–1 μg L−1 6-PPDQ, 10 μg L−1 6-PPDQ downregulated the expression of genes involved in PINK1/Parkin-dependent mitophagy (pink-1, pdr-1, and sqst-1) and receptor-mediated mitophagy (fndc-1 and dct-1). RNAi of these mitophagy-related genes enhanced the 6-PPDQ toxicity on mitochondrial function and lifespan. Moreover, after 6-PPDQ (10 μg L−1) exposure, 6-PPDQ could be accumulated in the nucleus and affected the expressions of some transcription factor (TF) genes (daf-5, elt-2, atf-7, daf-16, bar-1, and skn-1) thereby inducing the inhibition of these two types of mitophagy. Inhibition in both mitophagy and the mitochondrial unfolded protein response (mt UPR) caused more severe 6-PPDQ toxicity on the mitochondrial function and lifespan. Our results demonstrate the crucial role of mitophagy suppression in mediating the toxicity of 6-PPDQ, which is useful for predicting the environmental exposure risk of 6-PPDQ on organisms.

Graphical abstract: An environmentally relevant concentration of 6-PPD quinone inhibits two types of mitophagy to cause mitochondrial dysfunction and lifespan reduction in Caenorhabditis elegans

Supplementary files

Article information

Article type
Paper
Submitted
24 Mar 2025
Accepted
23 May 2025
First published
09 Jun 2025

Environ. Sci.: Processes Impacts, 2025,27, 1928-1940

An environmentally relevant concentration of 6-PPD quinone inhibits two types of mitophagy to cause mitochondrial dysfunction and lifespan reduction in Caenorhabditis elegans

X. Hua and D. Wang, Environ. Sci.: Processes Impacts, 2025, 27, 1928 DOI: 10.1039/D5EM00224A

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