Article
Mitochondrial translational defect extends lifespan in C. elegans by activating UPRmt
Published in
Redox Biology
Abstract
How mitochondrial translation shapes organismal aging is only partly understood. Using Caenorhabditis elegans, the authors examined threonyl-tRNA synthetase (TARS-1), an enzyme that supports mitochondrial protein synthesis. A single tars-1 gene was shown to encode both cytoplasmic and mitochondrial versions of the enzyme through translational reinitiation. Losing the mitochondrial form reduced charging of mitochondrial tRNA-Thr, weakened mitochondrial translation, and compromised respiration. Unexpectedly, these defects switched on the mitochondrial unfolded protein response (UPRmt), which extended lifespan even though development and locomotion were impaired. The results forge a direct link between tRNA charging, mitochondrial translation, stress signaling, and longevity.
Results
• One tars-1 gene yields both cytoplasmic and mitochondrial threonyl-tRNA synthetases via translational reinitiation.
• Mitochondrial TARS-1 loss lowers mitochondrial tRNA-Thr charging efficiency.
• Reduced charging impairs mitochondrial protein translation and respiratory chain function.
• Mitochondrial tars-1 knockdown decreases oxygen consumption and complex I activity.
• Defective mitochondrial translation activates UPRmt.
• Mitochondrial tars-1 deficiency delays development, curbs reproduction, and hampers locomotion.
• Despite these deficits, UPRmt activation markedly extends lifespan.
• Loss of several other mitochondrial aminoacyl-tRNA synthetases similarly triggers UPRmt, implying a conserved link between mitochondrial tRNA charging and stress signaling.
Fig. 1. Reduced mitochondrial tRNA-Thr charging impairs mitochondrial translation, activates UPRmt, and extends lifespan in C. elegans.
Conclusion
Mitochondrial tRNA charging emerges from this work as a critical control point for mitochondrial function and aging. Loss of mitochondrial TARS-1 reduces tRNA-Thr aminoacylation and mitochondrial translation, producing respiratory defects that activate the protective UPRmt program. This stress response extends longevity even as mitochondrial performance declines. The findings establish tRNA charging as a regulatory layer that connects mitochondrial protein synthesis, cellular stress adaptation, and lifespan control, and they position aminoacyl-tRNA synthetases as key modulators of organismal aging.
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