Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans
Abstract
Marked alterations in cellular energy metabolism are a universal hallmark of the ageing process. The biogenesis and function of mitochondria, the energy-generating organelles in eukaryotic cells, are primary longevity determinants. Genetic or pharmacological manipulations of mitochondrial activity profoundly affect the lifespan of diverse organisms. However, the molecular mechanisms regulating mitochondrial biogenesis and energy metabolism during ageing are poorly understood. Prohibitins are ubiquitous, evolutionarily conserved proteins, which form a ring-like, high-molecular-mass complex at the inner membrane of mitochondria. Here, we show that the mitochondrial prohibitin complex promotes longevity by modulating mitochondrial function and fat metabolism in the nematode Caenorhabditis elegans. We found that prohibitin deficiency shortens the lifespan of otherwise wild-type animals. Notably, knockdown of prohibitin promotes longevity in diapause mutants or under conditions of dietary restriction. In addition, prohibitin deficiency extends the lifespan of animals with compromised mitochondrial function or fat metabolism. Depletion of prohibitin influences ATP levels, animal fat content and mitochondrial proliferation in a genetic-background- and age-specific manner. Together, these findings reveal a novel mechanism regulating mitochondrial biogenesis and function, with opposing effects on energy metabolism, fat utilization and ageing in C. elegans. Prohibitin may have a similar key role in modulating energy metabolism during ageing in mammals.
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A hallmark of aging is the presence of a decline in mitochondrial function in skeletal muscle associated with accumulation of mitochondrial damage, abundant morphological alterations in mitochondria, reduced mitochondrial respiration, and increased oxidative stress.
“A hallmark of aging is the presence of a decline in mitochondrial function in skeletal muscle associated with accumulation of mitochondrial damage, abundant morphological alterations in mitochondria (e.g., rounded and giant mitochondria), reduced mitochondrial respiration, and increased oxidative stress (Shigenaga et al, 1994; Preston et al, 2008; Artal‐Sanz & Tavernarakis, 2009; Bratic & Larsson,”
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“Prohibitins are ubiquitous, evolutionary conserved proteins that form a ring-like complex at the inner membrane of the mitochondria (Artal-Sanz and Tavernarakis, 2009).”
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- Authors
- Artal-Sanz, M., & Tavernarakis, N.
- Affiliations
- Foundation for Research and Technology Hellas (GR)
- Corresponding author
- Tavernarakis, Nektarios
- Venue
- Nature
- Published
- 2009-10
- Volume
- 461
- Issue
- 7265
- Pages
- 793-797
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1979705235
- Cited by
- 196
- References
- 4
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 13 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 17 · 2015: 14 · 2014: 19 · 2013: 13 · 2012: 16
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Institutes of Health
- National Center for Research Resources
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- prohibitin, aging, lifespan extension, Caenorhabditis elegans, diapause, dietary restriction, mitochondrial biogenesis, mitochondrial function, fat metabolism, energy metabolism, ATP levels, mitochondrial proliferation, fat content
- MeSH terms
- Prohibitins, Adenosine Triphosphate, Aging, Animals, Energy Metabolism, Intestinal Mucosa, Longevity, Mitochondria, Mutation, Repressor Proteins, Signal Transduction, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Caloric Restriction, Lipid Metabolism, Gene Knockdown Techniques
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