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Evidence for the involvement of lipid rafts localized at the ER-mitochondria associated membranes in autophagosome formation.
- Source :
-
Autophagy [Autophagy] 2016 Jun 02; Vol. 12 (6), pp. 917-35. Date of Electronic Publication: 2016 Apr 28. - Publication Year :
- 2016
-
Abstract
- Mitochondria-associated membranes (MAMs) are subdomains of the endoplasmic reticulum (ER) that interact with mitochondria. This membrane scrambling between ER and mitochondria appears to play a critical role in the earliest steps of autophagy. Recently, lipid microdomains, i.e. lipid rafts, have been identified as further actors of the autophagic process. In the present work, a series of biochemical and molecular analyses has been carried out in human fibroblasts with the specific aim of characterizing lipid rafts in MAMs and to decipher their possible implication in the autophagosome formation. In fact, the presence of lipid microdomains in MAMs has been detected and, in these structures, a molecular interaction of the ganglioside GD3, a paradigmatic "brick" of lipid rafts, with core-initiator proteins of autophagy, such as AMBRA1 and WIPI1, was revealed. This association seems thus to take place in the early phases of autophagic process in which MAMs have been hypothesized to play a key role. The functional activity of GD3 was suggested by the experiments carried out by knocking down ST8SIA1 gene expression, i.e., the synthase that leads to the ganglioside formation. This experimental condition results in fact in the impairment of the ER-mitochondria crosstalk and the subsequent hindering of autophagosome nucleation. We thus hypothesize that MAM raft-like microdomains could be pivotal in the initial organelle scrambling activity that finally leads to the formation of autophagosome.
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Autophagosomes ultrastructure
Autophagy
Calnexin metabolism
Endoplasmic Reticulum ultrastructure
Fibroblasts metabolism
GTP Phosphohydrolases genetics
GTP Phosphohydrolases metabolism
Gangliosides metabolism
Gene Expression Regulation
Gene Knockdown Techniques
Humans
Mitochondria ultrastructure
Mitochondrial Membranes ultrastructure
Mitochondrial Proteins genetics
Mitochondrial Proteins metabolism
Protein Binding
Sialyltransferases metabolism
Autophagosomes metabolism
Endoplasmic Reticulum metabolism
Membrane Microdomains metabolism
Mitochondria metabolism
Mitochondrial Membranes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-8635
- Volume :
- 12
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Autophagy
- Publication Type :
- Academic Journal
- Accession number :
- 27123544
- Full Text :
- https://doi.org/10.1080/15548627.2016.1160971