AMPK contributes to autophagosome maturation and lysosomal fusion

Jang, Minsu; Park, Rackhyun; Kim, Hyun-Ju; Namkoong, Sim; Jo, Daum; Huh, Yang Hoon; Jang, Ik Soon; Lee, Jin I.; Park, Junsoo

doi:10.1038/s41598-018-30977-7

Cited by 108 publications

(85 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VEGF did not induce LC3B conjugation in cells, in which AMPKα1 or AMPKα2 were downregulated ( Figure 3E,F). However, under these conditions, we observed an increased basal expression and conjugation of LC3B compared to control cells as reported previously [67,68] ( Figure 3E-G). This was not accompanied by an alteration of the basal autophagic flux in AMPKα1-or AMPKα2-depleted cells ( Figure 3H,I).…”

Section: Vegf-induced Initiation Of Autophagy Depends On Ampkα1supporting

confidence: 91%

VEGF Triggers Transient Induction of Autophagy in Endothelial Cells via AMPKα1

Spengler

Kryeziu

Größe

et al. 2020

Cells

View full text Add to dashboard Cite

AMP-activated protein kinase (AMPK) is activated by vascular endothelial growth factor (VEGF) in endothelial cells and it is significantly involved in VEGF-induced angiogenesis. This study investigates whether the VEGF/AMPK pathway regulates autophagy in endothelial cells and whether this is linked to its pro-angiogenic role. We show that VEGF leads to AMPKα1-dependent phosphorylation of Unc-51-like kinase 1 (ULK1) at its serine residue 556 and to the subsequent phosphorylation of the ULK1 substrate ATG14. This triggers initiation of autophagy as shown by phosphorylation of ATG16L1 and conjugation of the microtubule-associated protein light chain 3B, which indicates autophagosome formation; this is followed by increased autophagic flux measured in the presence of bafilomycin A1 and by reduced expression of the autophagy substrate p62. VEGF-induced autophagy is transient and probably terminated by mechanistic target of rapamycin (mTOR), which is activated by VEGF in a delayed manner. We show that functional autophagy is required for VEGF-induced angiogenesis and may have specific functions in addition to maintaining homeostasis. In line with this, inhibition of autophagy impaired VEGF-mediated formation of the Notch intracellular domain, a critical regulator of angiogenesis. Our study characterizes autophagy induction as a pro-angiogenic function of the VEGF/AMPK pathway and suggests that timely activation of autophagy-initiating pathways may help to initiate angiogenesis.

show abstract

Section: Vegf-induced Initiation Of Autophagy Depends On Ampkα1supporting

confidence: 91%

VEGF Triggers Transient Induction of Autophagy in Endothelial Cells via AMPKα1

Spengler

Kryeziu

Größe

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Although ROS can indirectly activate AMPK through increases in AMP, a few studies have demonstrated that ROS can modulate AMPK activity by direct posttranslational modification . Recent study suggests that the α1 isoform of AMPK is essential for efficient AP maturation and fusion with lysosomes …”

Section: Molecular Regulation Of Autophagy Machinerymentioning

confidence: 99%

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Al‐Bari

2020

Annals of the New York Academy of Sciences

206

109

View full text Add to dashboard Cite

Macroautophagy is a lysosomal degradative pathway or recycling process that maintains cellular homeostasis. This autophagy involves a series of sequential processing events, such as initiation; elongation and nucleation of the isolation membrane; cargo recruitment and maturation of the autophagosome (AP); transport of the AP; docking and fusion of the AP with a late endosome or lysosome; and regeneration of the lysosome by the autophagic lysosomal reformation cycle. These events are critically coordinated by the action of a set of several key components, including autophagy‐related proteins (Atg), and regulated by intricate networks, such as mechanistic target of rapamycin (mTOR), a master regulator of autophagy, as well as mTOR‐independent signaling pathways. Among mTOR‐independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy. This review discusses the recent advances in elucidating the molecular mechanisms and regulation of the autophagy process. Understanding these mechanisms may ultimately allow scientists and clinicians to control this process in order to improve human health.

show abstract

“…ey also demonstrated that the decreased autolysosome formation is related to decreased autophagosome fusion with lysosomes in AMPKα1 knockout cells [69]. ese shreds of evidence show that AMPK activation is important not only in autophagosome formation but also in autophagosome clearance and can improve the overall autophagic clearance of aberrant proteins.…”

Section: Ampk and Aβ Metabolismmentioning

confidence: 91%

The Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence

Assefa

Tafere

Wondafrash

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Alzheimer’s disease is a multifactorial neurodegenerative disease characterized by progressive cognitive dysfunction. It is the most common form of dementia. The pathologic hallmarks of the disease include extracellular amyloid plaque, intracellular neurofibrillary tangles, and oxidative stress, to mention some of them. Despite remarkable progress in the understanding of the pathogenesis of the disease, drugs for cure or disease-modifying therapy remain somewhere in the distance. From recent time, the signaling molecule AMPK is gaining enormous attention in the AD drug research. AMPK is a master regulator of cellular energy metabolism, and recent pieces of evidence show that perturbation of its function is highly ascribed in the pathology of AD. Several drugs are known to activate AMPK, but their effect in AD remains to be controversial. In this review, the current shreds of evidence on the effect of AMPK activators in Aβ accumulation, tau aggregation, and oxidative stress are addressed. Positive and negative effects are reported with regard to Aβ and tauopathy but only positive in oxidative stress. We also tried to dissect the molecular interplays where the bewildering effects arise from.

show abstract

AMPK contributes to autophagosome maturation and lysosomal fusion

Cited by 108 publications

References 33 publications

VEGF Triggers Transient Induction of Autophagy in Endothelial Cells via AMPKα1

VEGF Triggers Transient Induction of Autophagy in Endothelial Cells via AMPKα1

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

The Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence

Contact Info

Product

Resources

About