Lifespan‐extending interventions enhance lipid‐supported mitochondrial respiration in Caenorhabditis elegans
| Autor: | Hugo Aguilaniu, Fernanda Marques da Cunha, Alicia J. Kowaltowski, Carolina Gomes de Assis, Alexia Buis, Talita Romanatto, Felipe Macedo |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Longevity Mutant Oxidative phosphorylation Mitochondrion Biochemistry Germline 03 medical and health sciences Adenosine Triphosphate Oxygen Consumption 0302 clinical medicine Lipid oxidation Organelle Genetics Animals Respiratory system Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Caloric Restriction 2. Zero hunger Electron Transport Complex I Bacteria biology Respiration biology.organism_classification Lipids Mitochondria Cell biology Oxidative Stress 030104 developmental biology Food Microbiology Energy Metabolism Food Deprivation 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | The FASEB Journal. 34:9972-9981 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201901880r |
| Popis: | Dietary restriction and reduced reproduction have been linked to long lifespans in the vast majority of species tested. Although decreased mitochondrial mass and/or function are hallmarks of aging, little is known about the mechanisms by which these organelles contribute to physiological aging or to the effects of lifespan-extending interventions, particularly with respect to oxidative phosphorylation and energy production. Here, we employed the nematode Caenorhabditis elegans to examine the effects of inhibition of germline proliferation and dietary restriction, both of which extend the lifespan of C. elegans, on mitochondrial respiratory activity in whole animals and isolated organelles. We found that oxygen consumption rates and mitochondrial mass were reduced in wild-type (WT) C. elegans subjected to bacterial deprivation (BD) compared with animals fed ad libitum (AL). In contrast, BD decreased the rate of oxygen uptake but not mitochondrial mass in germline-less glp-1(e2144ts) mutants. Interestingly, mitochondria isolated from animals subjected to BD and/or inhibition of germline proliferation showed no differences in complex I-mediated respiratory activity compared to control mitochondria, whereas both interventions enhanced the efficiency with which mitochondria utilized lipids as respiratory substrates. Notably, the combination of BD and inhibition of germline proliferation further increased mitochondrial lipid oxidation compared to either intervention alone. We also detected a striking correlation between lifespan extension in response to BD and/or inhibition of germline proliferation and the capacity of C. elegans to generate ATP from lipids. Our results thus suggest that the ability to oxidize lipids may be determinant in enhanced longevity. |
| Databáze: | OpenAIRE |
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