Autophagy regulator Atg9 is degraded by the proteasome

Hu, Guohui; Rios, Lizette E.; Yan, Zheng; Jasper, Angela M.; Luera, Dezzarae; Luo, Shuhong; Rao, Hai

doi:10.1016/j.bbrc.2019.11.089

Cited by 19 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This fits with recent evidence showing that UPS activity, rather than inhibition, promotes autophagy both by fostering the nuclear translocation of TFEB, and remarkably, by degrading mTOR itself, leading to its downregulation and detachment from the lysosomes [111]. In baseline conditions the turnover of the transmembrane autophagy protein Atg9 is also carried out by the UPS, while this is impeded upon autophagy-inducing stimuli such as starvation or rapamycin treatment [112]. Likewise, upon ubiquitination by the ubiquitin-activating enzyme UBA6 and the ubiquitin-conjugating enzyme/ubiquitin ligase BIRC6, LC3-II is targeted for UPS degradation [115,116].…”

Section: Emerging Mechanisms Underlying Autophagy and Proteasome Crossupporting

confidence: 90%

“…In this functional setting, the merging between UPS and autophagy is defined as "proteaphagy". This is in line with studies indicating a reciprocal regulation between the two cell-clearing systems, with UPS behaving as a sentinel in sensing and regulating autophagy, and vice versa [68,[108][109][110][111][112][113]. In detail, UPS regulates the duration and amplitude of the autophagy response by controlling the stability of Unc-51 like autophagy activating kinase (ULK1)/Atg1 complex as well as mTOR and transcription factor EB (TFEB) kinases [108][109][110].…”

Section: Emerging Mechanisms Underlying Autophagy and Proteasome Crossupporting

confidence: 86%

See 1 more Smart Citation

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

Limanaqi

Biagioni

Gambardella

et al. 2020

IJMS

View full text Add to dashboard Cite

Alterations in autophagy and the ubiquitin proteasome system (UPS) are commonly implicated in protein aggregation and toxicity which manifest in a number of neurological disorders. In fact, both UPS and autophagy alterations are bound to the aggregation, spreading and toxicity of the so-called prionoid proteins, including alpha synuclein (α-syn), amyloid-beta (Aβ), tau, huntingtin, superoxide dismutase-1 (SOD-1), TAR-DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS). Recent biochemical and morphological studies add to this scenario, focusing on the coordinated, either synergistic or compensatory, interplay that occurs between autophagy and the UPS. In fact, a number of biochemical pathways such as mammalian target of rapamycin (mTOR), transcription factor EB (TFEB), Bcl2-associated athanogene 1/3 (BAG3/1) and glycogen synthase kinase beta (GSk3β), which are widely explored as potential targets in neurodegenerative proteinopathies, operate at the crossroad between autophagy and UPS. These biochemical steps are key in orchestrating the specificity and magnitude of the two degradation systems for effective protein homeostasis, while intermingling with intracellular secretory/trafficking and inflammatory pathways. The findings discussed in the present manuscript are supposed to add novel viewpoints which may further enrich our insight on the complex interactions occurring between cell-clearing systems, protein misfolding and propagation. Discovering novel mechanisms enabling a cross-talk between the UPS and autophagy is expected to provide novel potential molecular targets in proteinopathies.

show abstract

Section: Emerging Mechanisms Underlying Autophagy and Proteasome Crossupporting

confidence: 90%

Section: Emerging Mechanisms Underlying Autophagy and Proteasome Crossupporting

confidence: 86%

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

Limanaqi

Biagioni

Gambardella

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Recently, it was found that two other Atg proteins are regulated by ubiquitination: Atg14 is degraded by the ubiquitin-proteasome system as a means to modulate autophagy activity [ 23 ], and Atg9 is degraded by the proteasome under normal conditions but stabilized upon starvation and rapamycin treatment [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

The yeast mitophagy receptor Atg32 is ubiquitinated and degraded by the proteasome

et al. 2020

View full text Add to dashboard Cite

Mitophagy, the process that degrades mitochondria selectively through autophagy, is involved in the quality control of mitochondria in cells grown under respiratory conditions. In yeast, the presence of the Atg32 protein on the outer mitochondrial membrane allows for the recognition and targeting of superfluous or damaged mitochondria for degradation. Post-translational modifications such as phosphorylation are crucial for the execution of mitophagy. In our study we monitor the stability of Atg32 protein in the yeast S. cerevisiae and show that Atg32 is degraded under normal growth conditions, upon starvation or rapamycin treatment. The Atg32 turnover can be prevented by inhibition of the proteasome activity, suggesting that Atg32 is also ubiquitinated. Mass spectrometry analysis of purified Atg32 protein revealed that at least lysine residue in position 282 is ubiquitinated. Interestingly, the replacement of lysine 282 with alanine impaired Atg32 degradation only partially in the course of cell growth, suggesting that additional lysine residues on Atg32 might also be ubiquitinated. Our results provide the foundation to further elucidate the physiological significance of Atg32 turnover and the interplay between mitophagy and the proteasome.

show abstract

“…The impaired UPS and autophagy defects also result in reduced clearance of tau tangles present in brains of AD patients, impairing the synapsis and cognition in patients [363]. Recent studies revealed important roles of UPS in regulating Atg9 availability, which in turn regulates autophagy progression [364]. In general, the nutrient status of a cell regulates UPS-dependent regulation of several cellular proteins and transcription factors that drive cell fate.…”

Section: Proteostasis Failure In Admentioning

confidence: 99%

Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease

Dhakal

Macreadie

2020

IJMS

View full text Add to dashboard Cite

Alzheimer’s Disease (AD) is a progressive multifactorial age-related neurodegenerative disorder that causes the majority of deaths due to dementia in the elderly. Although various risk factors have been found to be associated with AD progression, the cause of the disease is still unresolved. The loss of proteostasis is one of the major causes of AD: it is evident by aggregation of misfolded proteins, lipid homeostasis disruption, accumulation of autophagic vesicles, and oxidative damage during the disease progression. Different models have been developed to study AD, one of which is a yeast model. Yeasts are simple unicellular eukaryotic cells that have provided great insights into human cell biology. Various yeast models, including unmodified and genetically modified yeasts, have been established for studying AD and have provided significant amount of information on AD pathology and potential interventions. The conservation of various human biological processes, including signal transduction, energy metabolism, protein homeostasis, stress responses, oxidative phosphorylation, vesicle trafficking, apoptosis, endocytosis, and ageing, renders yeast a fascinating, powerful model for AD. In addition, the easy manipulation of the yeast genome and availability of methods to evaluate yeast cells rapidly in high throughput technological platforms strengthen the rationale of using yeast as a model. This review focuses on the description of the proteostasis network in yeast and its comparison with the human proteostasis network. It further elaborates on the AD-associated proteostasis failure and applications of the yeast proteostasis network to understand AD pathology and its potential to guide interventions against AD.

show abstract

Autophagy regulator Atg9 is degraded by the proteasome

Cited by 19 publications

References 28 publications

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

The yeast mitophagy receptor Atg32 is ubiquitinated and degraded by the proteasome

Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease

Contact Info

Product

Resources

About