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Splicing factor PRP-19 regulates mitochondrial stress response
Peixue Xia1,2, Liankui Zhou1,2, Jialiang Guan3
1State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Life Metabolism
|January 28, 2025
Summary
Splicing factors like PRP-19 are crucial for the mitochondrial unfolded protein response (UPRmt) in animals. This discovery reveals a conserved pathway linking mitochondrial health, immunity, and longevity.
Area of Science:
- Cellular Biology
- Genetics
- Aging Research
Background:
- Mitochondrial perturbation triggers the mitochondrial unfolded protein response (UPRmt) to maintain cellular homeostasis.
- UPRmt activation in *C. elegans* is linked to innate immunity and extended lifespan.
Purpose of the Study:
- To investigate the role of splicing factors in the UPRmt pathway.
- To determine if splicing factors influence UPRmt-mediated immune response and lifespan extension.
Main Methods:
- Utilized *Caenorhabditis elegans* as a model organism.
- Investigated the function of splicing factor Precursor RNA processing 19 (PRP-19).
- Performed knockdown experiments in mammalian cells to assess conserved mechanisms.
Main Results:
- Splicing factor PRP-19 is essential for UPRmt induction in *C. elegans*.
- PRP-19 modulates the innate immune response and lifespan extension triggered by mitochondrial stress.
- PRP-19 knockdown in mammalian cells impairs UPRmt activation and mitochondrial network integrity.
Conclusions:
- Splicing factors play a critical, evolutionarily conserved role in maintaining mitochondrial homeostasis.
- PRP-19 links mitochondrial health to innate immunity and organismal lifespan.
- This study uncovers a novel mechanism regulating mitochondrial function and stress response.
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