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NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin
Rebecca George Tharyan1, Andrea Annibal1, Isabelle Schiffer1,2
1Max Planck Institute for Biology of Ageing, Cologne, Germany.
Nature Metabolism
|July 23, 2020
Summary
Nuclear transcription factor NFYB-1 regulates mitochondrial function and organismal longevity. Its loss impacts mitochondrial health, but limiting prosaposin restores function, revealing a key signaling axis.
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- Mitochondria are vital organelles for cellular vitality and organismal longevity.
- Regulatory mechanisms governing mitochondrial function across different organizational levels are not fully understood.
- The NF-Y transcriptional complex plays a role in cellular processes.
Purpose of the Study:
- To investigate the role of Caenorhabditis elegans nuclear transcription factor Y, beta subunit (NFYB-1) in regulating mitochondrial function.
- To elucidate the molecular mechanisms by which NFYB-1 influences mitochondrial health and organismal longevity.
- To identify novel pathways connecting nuclear transcription, lysosomal function, and mitochondrial homeostasis.
Main Methods:
- RNA interference (RNAi) screens to identify regulators of mitochondrial function.
- Analysis of mitochondrial gene expression, oxygen consumption, and morphology.
- Multi-omics analysis to identify NFYB-1 targets and associated pathways.
- Genetic manipulation and biochemical assays to assess the role of prosaposin and cardiolipin.
Main Results:
- NFYB-1 loss disrupts mitochondrial gene expression, reduces oxygen consumption, causes mitochondrial fragmentation, and impairs organismal longevity.
- NFYB-1 acts as a repressor of lysosomal prosaposin, a regulator of glycosphingolipid metabolism.
- Reducing prosaposin expression or supplementing cardiolipin rescues mitochondrial function and longevity in nfyb-1 mutants.
Conclusions:
- NFYB-1 is a critical regulator of mitochondrial function and organismal longevity in C. elegans.
- The NFYB-1-prosaposin axis coordinates lysosomal to mitochondria signaling through lipid metabolism.
- This axis represents a novel pathway for enhancing cellular mitochondrial function and promoting organismal health.
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