c-Flip KO fibroblasts display lipid accumulation associated with endoplasmic reticulum stress

Biochimica Et Biophysica Acta
Claudia GiampietriElio Ziparo

Abstract

c-Flip proteins are well-known apoptosis modulators. They generally contribute to tissue homeostasis maintenance by inhibiting death-receptor-mediated cell death. In the present manuscript, we show that c-Flip knock-out (KO) mouse embryonic fibroblasts (MEFs) kept in culture under starvation conditions gradually modify their phenotype and accumulate vacuoles, becoming progressively larger according to the duration of starvation. Large vacuoles are present in KO MEFs though not in WT MEFs, and are Oil Red-O positive, which indicates that they represent lipid droplets. Western blot experiments reveal that, unlike WT MEFs, KO MEFs express high levels of the lipogenic transcription factor PPAR-γ. Lipid droplet accumulation was found to be associated with endoplasmic reticulum (ER) stress activation and autophagic modulation valuated by means of BIP increase, LC3 lipidation and AMP-activated protein kinase (AMPK) phosphorylation, and p62 accumulation. Interestingly, XBP-1, an ER stress-induced lipogenic transcription factor, was found to preferentially localize in the nucleus rather than in the cytoplasm of KO MEFs. These data demonstrate that, upon starvation, c-Flip affects lipid accumulation, ER stress and autophagy, thereby poin...Continue Reading

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Citations

Jun 9, 2016·Cellular Signalling·Silvia ContiElio Ziparo
Jun 16, 2017·International Journal of Molecular Sciences·Claudia GiampietriElio Ziparo
May 29, 2018·The FEBS Journal·Luke HumphreysDaniel B Longley
Mar 11, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Lingjie KongHongcheng Zhang

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