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| Status |
Public on Jun 07, 2021 |
| Title |
Nuclear receptor NHR-49 promotes peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency in C. elegans |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The intracellular level of fatty aldehydes is tightly regulated to minimize the formation of toxic aldehyde adducts of cellular components. Accordingly, deficiency of a fatty aldehyde dehydrogenase FALDH causes the neurologic disorder Sjögren-Larsson syndrome (SLS) in humans. However, cellular responses to unresolved, elevated fatty aldehyde levels are poorly understood. Based on lipidomic and imaging analysis, we report that the loss of endoplasmic reticulum-, mitochondria- and peroxisomes-associated ALH-4, the C. elegans FALDH ortholog, increases fatty aldehyde levels and reduces fat storage. ALH-4 deficiency in the intestine, cell-nonautonomously induces NHR-49/NHR-79-dependent hypodermal peroxisome proliferation. This is accompanied by the upregulation of catalases and fatty acid catabolic enzymes, as indicated by RNA sequencing. Such a response is required to counteract ALH-4 deficiency since alh-4; nhr-49 double mutant animals are not viable. Our work reveals unexpected inter-tissue communication of fatty aldehyde levels, and suggests pharmacological modulation of peroxisome proliferation as a therapeutic strategy for SLS.
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| Overall design |
RNA-seq with three biological replicates of synchronized wild type N2 and mutant alh-4(-) worms at the L4 stage to determine the differentially expressed genes.
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| Contributor(s) |
Zeng L, Preusch CB, He GJ, Cheung TH, Mak HY |
| Citation(s) |
34237064 |
| |
| Submission date |
Dec 07, 2020 |
| Last update date |
Aug 03, 2021 |
| Contact name |
Ho Yi Mak |
| E-mail(s) |
[email protected]
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| Organization name |
The Hong Kong University of Science and Technology
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| Department |
Division of Life Science
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| Lab |
Mak Lab
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| Street address |
Clear Water Bay
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| City |
Hong Kong |
| ZIP/Postal code |
NA |
| Country |
China |
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| Platforms (1) |
| GPL19757 |
Illumina NextSeq 500 (Caenorhabditis elegans) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA683027 |
| SRA |
SRP296805 |
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