Distinct metabolic alterations in different Caenorhabditis elegans mitochondrial mutants

Mitochondria play an essential role in various biochemical processes that maintain cellular homeostasis. Minor defects in the mitochondrial genome can lead to aversive behavioral responses in an organism. Nevertheless, little is known about the impact of mitochondrial mutations on the metabolome of Caenorhabditis elegans (C. elegans). In this study, an untargeted metabolomics approach was employed to elucidate the metabolic aberrant caused by mitochondrial DNA mutations in C. elegans. Specifically, three mutant strains of C. elegans, including clk-1, mev-1, andphb-2, were adopted to study corresponding metabolic signatures. Adult worms were collected, and metabolites were extracted and analyzed by gas chromatography-mass spectrometry. Uni-and multivariate analyses were performed to elucidate perturbed metabolism between wildtype worms and mutant strains, and metabolic differences among the mutants. The tricarboxylic acid cycle intermediates, amino acids, and sugars were significantly affected in the mitochondrial mutants. Overall, each mitochondrial DNA mutation exhibited a different pattern of metabolic alterations. The shift of metabolome appeared to be associated with the lifespan of C. elegans. In particular, clk-1 and mev-1 strains, which had the opposite phenotypes of lifespan, had apparently different metabolomes. Our findings set light on the metabolic consequences of mitochondrial genetic variants, which may help better understand mitochondrial disease mechanisms.

Automated summary

This study investigated the metabolic consequences of mitochondrial DNA mutations in C. elegans using an untargeted metabolomics approach. Three mutant strains (clk-1, mev-1, and phb-2) exhibited significant metabolic differences compared to the wildtype worms, with distinct patterns of metabolic alterations observed in each mutant strain. The metabolome changes appeared to be correlated with the lifespan of C. elegans, with clk-1 and mev-1 strains showing different metabolomes despite having opposite lifespan phenotypes. These findings shed light on the metabolic effects of mitochondrial genetic variants and may contribute to a better understanding of mitochondrial disease mechanisms.