3D tomography reveals connections between the phagophore and endoplasmic reticulum

Ylä-Anttila, Päivi; Vihinen, Helena; Jokitalo, Eija; Eskelinen, Eeva‐Liisa

doi:10.4161/auto.5.8.10274

Cited by 593 publications

(482 citation statements)

References 20 publications

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“…These were named omegasomes, as DFCP1-positive rings often looked like Ω-shaped structures on the ER. The connection between isolation membranes and the ER was further confirmed by two independent studies using 3D tomographic imaging of isolation membranes [64,65]. These studies have shown that the cupshaped isolation membrane was tightly sandwiched by two sheets of ER.…”

Section: Autophagosome Formation On the Ersupporting

confidence: 49%

A current perspective of autophagosome biogenesis

2013

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Autophagy is a bulk degradation system induced by cellular stresses such as nutrient starvation. Its function relies on the formation of double-membrane vesicles called autophagosomes. Unlike other organelles that appear to stably exist in the cell, autophagosomes are formed on demand, and once their formation is initiated, it proceeds surprisingly rapidly. How and where this dynamic autophagosome formation takes place has been a long-standing question, but the discovery of Atg proteins in the 1990's significantly accelerated our understanding of autophagosome biogenesis. In this review, we will briefly introduce each Atg functional unit in relation to autophagosome biogenesis, and then discuss the origin of the autophagosomal membrane with an introduction to selected recent studies addressing this problem.

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Section: Autophagosome Formation On the Ersupporting

confidence: 49%

A current perspective of autophagosome biogenesis

2013

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“…Membranes derived from the Golgi, endoplasmic reticulum, mitochondria, and plasma membrane have been implicated as the source membranes. [20][21][22][23][24][25] It is possible that vesicles from multiple membrane sources may fuse heterotypically to generate APs. This early fusion steps may involve lipidhydrolyzing enzymes, possibly PLD.…”

Section: Discussionmentioning

confidence: 99%

Phospholipase D1 regulates autophagic flux and clearance of α-synuclein aggregates

et al. 2014

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Many neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by abnormal accumulations of aggregated proteins. Brains in these diseases also show accumulation of autophagic vesicles in the neuronal cytoplasm, suggesting impairment of the autophagic process. As autophagy involves de novo membrane production and vesicle fusion, extensive changes in lipid molecules are necessary. However, the involvement of signaling lipid-modifying enzymes in autophagy and their roles in neurodegenerative diseases are not clear. Using specific inhibitor, we show that loss of phospholipase D1 (PLD1) activity resulted in an accumulation of microtubule-associated protein light chain 3 (LC3), p62, and polyubiquitinated proteins, signs representing malfunction in autophagic flux. Fluorescence and electron microscopic analyses demonstrated impaired fusion of autophagosomes with lysosomes, resulting in accumulation of autophagosomes. Within the cells with impaired autophagic flux, a-synuclein aggregates accumulated in autophagosomes. Knockdown of PLD1 expression using small interfering RNA also resulted in impaired autophagic flux and accumulation of a-synuclein aggregates in autophagosomes. Neuronal toxicity caused by a-synuclein accumulation was rescued by overexpression of PLD1; however, expression of activity-deficient mutant, PLD1-KRM, showed reduced rescue effects. Finally, we demonstrated that both PLD activity and expression levels were reduced in brain tissues of dementia with Lewy bodies (DLB) patients, whereas the amounts of a-synuclein and p62 were increased in the same tissue samples. Collectively, these results suggest that insufficient PLD activity, and therefore, the changes in phospholipid compositions within membranes, might be an important contributor to impaired autophagic process and protein accumulation in Lewy body diseases.

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“…Both rough ER and the outer nuclear leaflet have been identified as autophagosome formation sites [13][14][15] , but these vesicles might also be generated at other places. Two ubiquitin-like systems are involved in autophagosome formation at these sites with Atg8 and Atg12 as the ubiquitin-like molecules at their center 16 .…”

Section: T Cells Detect Infected or Transformed Cells Via Antigen Prementioning

confidence: 99%

MHC presentation via autophagy and how viruses escape from it

Gannagé

Münz

2010

Semin Immunopathol

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T cells detect infected and transformed cells via antigen presentation by major histocompatibility complex (MHC) molecules on the cell surface. For T cell stimulation, these MHC molecules present fragments of proteins that are expressed or taken up by the cell. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8(+) and on MHC class II molecules to helper CD4(+) T cells. Proteasomes are primarily involved in MHC class I ligand and lysosomes, in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape and could maybe be harnessed for immunotherapy. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8 + and on MHC class II molecules to helper CD4 + T cells.Proteasomes are primarily involved in MHC class I ligand, and lysosomes in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes, and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape, and could maybe be harnessed for immunotherapy. Gannage and Münz 3

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3D tomography reveals connections between the phagophore and endoplasmic reticulum

Cited by 593 publications

References 20 publications

A current perspective of autophagosome biogenesis

A current perspective of autophagosome biogenesis

Phospholipase D1 regulates autophagic flux and clearance of α-synuclein aggregates

MHC presentation via autophagy and how viruses escape from it

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