DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans
| Autor: | Ramesh Ratnappan, Elizabeth Marie Steenkiste, Francis Raj Gandhi Amrit, Dennis Kostka, Judith L. Yanowitz, Carissa Perez Olsen, Shaw-Wen Chen, T. Brooke McClendon, Arjumand Ghazi |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Physiology Ribosome biogenesis Gene Expression Biochemistry Germline Fats 0302 clinical medicine RNA interference Animal Cells Immune Physiology Medicine and Health Sciences Homeostasis Genetics (clinical) Caenorhabditis elegans media_common 2. Zero hunger Regulation of gene expression Genetics Immune System Proteins biology Receptors Notch Reproduction Fatty Acids Longevity Gene Expression Regulation Developmental Forkhead Transcription Factors Adaptation Physiological Lipids Up-Regulation Nucleic acids Genetic interference OVA Epigenetics Cellular Types Research Article lcsh:QH426-470 media_common.quotation_subject Immunology Down-Regulation Antibodies 03 medical and health sciences Daf-16 Animals Adults Caenorhabditis elegans Proteins Molecular Biology Transcription factor Ecology Evolution Behavior and Systematics Triglycerides Biology and life sciences Correction Proteins Lipid metabolism Cell Biology biology.organism_classification Lipid Metabolism Peptide Elongation Factors Diet lcsh:Genetics 030104 developmental biology Fertility Germ Cells Age Groups Protein Biosynthesis Mutation People and Places Oocytes RNA Population Groupings Transcriptome 030217 neurology & neurosurgery |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 12, Iss 2, p e1005788 (2016) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti-longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation. Author Summary The balance between production and breakdown of fats is critical for health, especially during reproduction-related changes such as onset of puberty or menopause. However, little is known about how animals retain a balanced metabolism when undergoing major life events. Here, we have used a C. elegans mutant that successfully adapts to loss of reproductive cells to address this question. Our data suggest that the conserved proteins DAF-16/FOXO3A and TCER-1/TCERG1 mediate a coordinated increase in fat synthesis and degradation when the reproductive cells are lost. This coupling likely helps the animal to manage the lipids that would have been deposited in eggs as yolk, thus preventing metabolic disarray. These proteins also inhibit processes that would have normally supported reproduction. Together the activities of these transcription regulators allow the mutant to convert a debilitating loss of fertility into improved health and longevity. We also report that TCER-1 promotes reproductive health in normal adults, whereas when procreation is impeded, it switches roles to repress fertility and enhance lipid equilibrium. These observations offer insights into how complex organisms coordinate their metabolism to suit their reproductive needs. |
| Databáze: | OpenAIRE |
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