Dataset Information
The role of FYCO1-dependent autophagy in lens fiber cell differentiation.
Ontology highlight
ABSTRACT: FYCO1 (FYVE and coiled-coil domain containing 1) is an adaptor protein, expressed ubiquitously and required for microtubule-dependent, plus-end-directed transport of macroautophagic/autophagic vesicles. We have previously shown that loss-of-function mutations in FYCO1 cause cataracts with no other ocular and/or extra-ocular phenotype. Here, we show fyco1 homozygous knockout (fyco1-/-) mice recapitulate the cataract phenotype consistent with a critical role of FYCO1 and autophagy in lens morphogenesis. Transcriptome coupled with proteome and metabolome profiling identified many autophagy-associated genes, proteins, and lipids respectively perturbed in fyco1-/- mice lenses. Flow cytometry of FYCO1 (c.2206C>T) knock-in (KI) human lens epithelial cells revealed a decrease in autophagic flux and autophagic vesicles resulting from the loss of FYCO1. Transmission electron microscopy showed cellular organelles accumulated in FYCO1 (c.2206C>T) KI lens-like organoid structures and in fyco1-/- mice lenses. In summary, our data confirm the loss of FYCO1 function results in a diminished autophagic flux, impaired organelle removal, and cataractogenesis.
INSTRUMENT(S): Q Exactive
PROVIDER: MTBLS206 | MetaboLights | 2024-03-24
REPOSITORIES: MetaboLights
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Publications
The role of FYCO1-dependent autophagy in lens fiber cell differentiation.
Autophagy 20220328 9
FYCO1 (FYVE and coiled-coil domain containing 1) is an adaptor protein, expressed ubiquitously and required for microtubule-dependent, plus-end-directed transport of macroautophagic/autophagic vesicles. We have previously shown that loss-of-function mutations in <i>FYCO1</i> cause cataracts with no other ocular and/or extra-ocular phenotype. Here, we show <i>fyco1</i> homozygous knockout (<i>fyco1<sup>-/-</sup></i>) mice recapitulate the cataract phenotype consistent with a critical role of FYCO ...[more]
