Hijacking intracellular membranes to feed autophagosomal growth

Staiano, Leopoldo; Zappa, Francesca

doi:10.1002/1873-3468.13637

Cited by 12 publications

(12 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first autophagy-related (ATG) gene was identified by the 2016 Nobel laureate Yoshinori Ohsumi in yeast in 1993. Now the number of ATG genes has increased to about 40 (Staiano and Zappa, 2019). Among them, the autophagy gene WDR45 (also known as WIPI4) was critical for the formation of the autophagosome (Bakula et al, 2017(Bakula et al, , 2018.…”

Section: Introductionmentioning

confidence: 99%

WDR45 Mutation Impairs the Autophagic Degradation of Transferrin Receptor and Promotes Ferroptosis

Xiong

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

WDR45 is an autophagy-related protein that involves in the formation of autophagosome. Mutations in WDR45 lead to the impairment of autophagy which is associated with the human β-propeller protein-associated neurodegeneration (BPAN). However, the relationship between autophagy and brain iron accumulation in patients with BPAN remains unclear. Here, we demonstrated that transferrin receptor (TfRC) which is critical for the iron import of cells was degraded via autophagy. TfRC was accumulated after the inhibition of autophagy by treatment with autophagic inhibitor chloroquine or knockdown of ATG2A. The intracellular iron content was increased in cells overexpressing TfRC or mutant WDR45, however, ferritin H (FTH) chain was decreased. Increased TfRC and simultaneously decreased FTH consequently resulted in an elevated level of ferrous iron (Fe2+) which further promoted cell ferroptosis, demonstrated by the increased lipid peroxidation and reactive oxygen species (ROS) and the decreased glutathione peroxidase 4 (GPX4) and cell viability. Taken together, these findings provide a piece of important evidence that WDR45 deficiency impairs autophagic degradation of TfRC, therefore leading to iron accumulation, and the elevated iron promotes ferroptosis which may contribute to the progression of BPAN.

show abstract

Section: Introductionmentioning

confidence: 99%

WDR45 Mutation Impairs the Autophagic Degradation of Transferrin Receptor and Promotes Ferroptosis

Xiong

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…The Golgi apparatus has been identified as a source of autophagosomal membranes, contributing to phagophore elongation through ATG16L recruitment (Itoh et al, 2008; Staiano and Zappa, 2019). To understand whether the GMAP210-dependent, IFT20-mediated recruitment of ATG16L1 to the Golgi is implicated to the pro-autophagic function of IFT20 we measured the autophagic flux in GMAP210KD cells.…”

Section: Resultsmentioning

confidence: 99%

The intraflagellar transport protein IFT20 recruits ATG16L1 to early endosomes to promote autophagosome formation in T cells

Finetti

Cassioli

Cianfanelli

et al. 2020

Preprint

View full text Add to dashboard Cite

Lymphocyte homeostasis, activation and differentiation crucially rely on basal autophagy. The fine-tuning of this process depends on autophagy-related (ATG) proteins and their interaction with the trafficking machinery that orchestrates the membrane rearrangements leading to autophagosome biogenesis. The underlying mechanisms are as yet not fully understood. The intraflagellar transport (IFT) system, known for its role in cargo transport along the axonemal microtubules of the primary cilium, has emerged as a regulator of autophagy in ciliated cells. Growing evidence indicates that ciliogenesis proteins participate in cilia-independent processes, including autophagy, in the non-ciliated T cell. Here we investigate the mechanism by which IFT20, an integral component of the IFT system, regulates basal T cell autophagy. We show that IFT20 interacts with the core autophagy protein ATG16L1 through its CC domain, which is also essential for its pro-autophagic activity. We demonstrate that IFT20 is required for the association of ATG16L1 with the Golgi complex and early endosomes, both of which have been identified as membrane sources for phagophore elongation. This involves the ability of IFT20 to interact with proteins that are resident at these subcellular localizations, namely the golgin GMAP210 at the Golgi apparatus and Rab5 at early endosomes. GMAP210 depletion, while leading to a dispersion of ATG16L1 from the Golgi, did not affect basal autophagy. Conversely, IFT20 was found to recruit ATG16L1 to early endosomes tagged for autophagosome formation by the BECLIN 1/VPS34/Rab5 complex, which resulted in the local accumulation of LC3. Hence IFT20 participates in autophagosome biogenesis under basal conditions by regulating the localization of ATG16L1 at early endosomes to promote autophagosome biogenesis. These data identify IFT20 as a new regulator of an early step of basal autophagy in T cells.

show abstract

“…Though the ER acts as an inexhaustible lipid pool, phagophore-localized de novo production of lipids by ER-resident lipid synthesis proteins is a significant contributor to phagophore expansion [ 73 , 74 ]. ERGIC (ER-Golgi intermediate compartment)-derived COPII (cytoplasmic coat protein complex II) vesicles and recycling endosome-derived vesicles positive for ATG9 and ATG16L1 contribute to, or even serve as the platform for, phagophore initiation and/or growth [ 4 , 53 , 75 , 76 , 77 , 78 ].…”

Section: Components Of the Autophagy Pathway From Nucleation To Fusionmentioning

confidence: 99%

Specific microRNAs for Modulation of Autophagy in Spinal Cord Injury

Visintin

Ray

2022

Brain Sciences

View full text Add to dashboard Cite

The treatment of spinal cord injury (SCI) is currently a major challenge, with a severe lack of effective therapies for yielding meaningful improvements in function. Therefore, there is a great opportunity for the development of novel treatment strategies for SCI. The modulation of autophagy, a process by which a cell degrades and recycles unnecessary or harmful components (protein aggregates, organelles, etc.) to maintain cellular homeostasis and respond to a changing microenvironment, is thought to have potential for treating many neurodegenerative conditions, including SCI. The discovery of microRNAs (miRNAs), which are short ribonucleotide transcripts for targeting of specific messenger RNAs (mRNAs) for silencing, shows prevention of the translation of mRNAs to the corresponding proteins affecting various cellular processes, including autophagy. The number of known miRNAs and their targets continues to grow rapidly. This review article aims to explore the relationship between autophagy and SCI, specifically with the intent of identifying specific miRNAs that can be useful to modulate autophagy for neuroprotection and the improvement of functional recovery in SCI.

show abstract

Hijacking intracellular membranes to feed autophagosomal growth

Cited by 12 publications

References 113 publications

WDR45 Mutation Impairs the Autophagic Degradation of Transferrin Receptor and Promotes Ferroptosis

WDR45 Mutation Impairs the Autophagic Degradation of Transferrin Receptor and Promotes Ferroptosis

The intraflagellar transport protein IFT20 recruits ATG16L1 to early endosomes to promote autophagosome formation in T cells

Specific microRNAs for Modulation of Autophagy in Spinal Cord Injury

Contact Info

Product

Resources

About