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Mitonuclear protein imbalance as a conserved longevity mechanism
Riekelt H Houtkooper1, Laurent Mouchiroud, Dongryeol Ryu
1Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Nature
|May 24, 2013
Summary
Mitochondrial ribosomal proteins (MRPs) regulate longevity by controlling the balance between nuclear and mitochondrial proteins. Disrupting this balance activates a key longevity pathway conserved across species.
Area of Science:
- Cellular Biology
- Genetics
- Aging Research
Background:
- Longevity is influenced by interconnected metabolic pathways.
- Mitochondrial function plays a critical role in aging and lifespan regulation.
Purpose of the Study:
- To identify key regulators of metabolism and longevity.
- To investigate the role of mitochondrial ribosomal proteins (MRPs) in aging.
Main Methods:
- Mouse population genetics and RNA interference in Caenorhabditis elegans.
- Pharmacological manipulation using antibiotics and ethidium bromide.
- Analysis of mitonuclear protein imbalance and the mitochondrial unfolded protein response (UPRmt).
Main Results:
- Mitochondrial ribosomal protein S5 (Mrps5) and other MRPs were identified as longevity regulators.
- Knockdown of MRPs induced mitonuclear protein imbalance, reduced respiration, and activated UPRmt.
- Antibiotics, ethidium bromide, resveratrol, and rapamycin mimicked MRP knockdown effects, extending lifespan by inducing mitonuclear imbalance and UPRmt.
Conclusions:
- MRPs are evolutionarily conserved regulators linking mitochondrial ribosomes to longevity pathways.
- Mitonuclear protein imbalance and UPRmt are conserved mechanisms of lifespan extension.
- Targeting mitochondrial translation and transcription can modulate aging.
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