Multimodal Nonlinear Optical Imaging of Subcellular Lipid and Vesicular Structures

Li, Xuesong; Lam, Wen Jiun; Cao, Zhe; Hao, Yan; Sun, Qiqi; He, Sicong; Mak, Ho Yi; Qu, Jianan Y.

doi:10.1364/ots.2016.oth4c.5

Cited by 1 publication

(1 citation statement)

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“…The attenuation of peroxisomal β-oxidation causes excess accumulation of TAG in expanded LDs in mutant animals that lack the DAF-22 thiolase (Zhang et al, 2010). This phenotype is most pronounced in the C. elegans intestine, which serves as a major fat storage tissue, and could be readily detected using quantitative Stimulated Raman Scattering (SRS) microscopy (Li et al, 2015) (Fig 1A). To identify genetic regulators of fat storage and LD expansion, we conducted a forward genetic screen for suppressor mutants that reversed the daf-22 mutant phenotypes.…”

Section: Molecular Cloning Of Alh-4mentioning

confidence: 99%

Nuclear receptor NHR-49 promotes peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency inC. elegans

Zeng

Preusch

et al. 2020

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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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Section: Molecular Cloning Of Alh-4mentioning

confidence: 99%