Activation and targeting of ATG8 protein lipidation

Martens, Sascha; Fracchiolla, Dorotea

doi:10.1038/s41421-020-0155-1

Cited by 144 publications

(110 citation statements)

References 180 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…In the cytosol, newly synthesized MAP1LC3B is cleaved by the autophagy-related 4B cysteine peptidase (ATG4B) at the C-terminal glycine residues 120 leading to MAP1LC3-I ( Figure 1). Phosphatidylethanolamine (PE)-conjugation of MAP1LC3-I resulting in the lipidated MAP1LC3-II form requires ATG7 and ATG3, as well as the ATG12-ATG5-ATG16L1 complex [45][46][47]. Formation of the latter involves conjugation of ATG12 to ATG5, in a process mediated by ATG7 and ATG10, and further binding of the ATG12-ATG5 conjugate to an ATG16L1 dimer.…”

Section: The Microtubule-associated Protein 1a/1b-light Chain 3 (Map1mentioning

confidence: 99%

Progress and Challenges in the Use of MAP1LC3 as a Legitimate Marker for Measuring Dynamic Autophagy In Vivo

Bonam

Bayry

Tschan

et al. 2020

Cells

View full text Add to dashboard Cite

Tremendous efforts have been made these last decades to increase our knowledge of intracellular degradative systems, especially in the field of autophagy. The role of autophagy in the maintenance of cell homeostasis is well documented and the existence of defects in the autophagic machinery has been largely described in diseases and aging. Determining the alterations occurring in the many forms of autophagy that coexist in cells and tissues remains complicated, as this cellular process is highly dynamic in nature and can vary from organ to organ in the same individual. Although autophagy is extensively studied, its functioning in different tissues and its links with other biological processes is still poorly understood. Several assays have been developed to monitor autophagy activity in vitro, ex vivo, and in vivo, based on different markers, the use of various inhibitors and activators, and distinct techniques. This review emphasizes the methods applied to measure (macro-)autophagy in tissue samples and in vivo via a protein, which centrally intervenes in the autophagy pathway, the microtubule-associated protein 1A/1B-light chain 3 (MAP1LC3), which is the most widely used marker and the first identified to associate with autophagosomal structures. These approaches are presented and discussed in terms of pros and cons. Some recommendations are provided to improve the reliability of the interpretation of results.

show abstract

Section: The Microtubule-associated Protein 1a/1b-light Chain 3 (Map1mentioning

confidence: 99%

Progress and Challenges in the Use of MAP1LC3 as a Legitimate Marker for Measuring Dynamic Autophagy In Vivo

Bonam

Bayry

Tschan

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…This suggests that the trafficking of surface proteins is influenced by the GABARAP subfamily in a far more general manner than supposed to date. The fact that some of the surface-located proteins identified during our proteomics study were up-regulated, while others were downregulated, is particularly interesting and most likely reflects the plethora of cellular processes that GABARAP-type proteins participate in, mainly as providing interaction platforms for protein complexes [ 52 , 53 , 54 , 55 ]. It must thus be considered that GABARAP-type protein deficiency provokes a pleiotropy of potentially counteracting effects.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent results from a yet unpublished study show altered surfaceome composition of Atg5 -/- mouse embryonic fibroblasts [ 57 ]. ATG5 is a key component of the LC3/GABARAP lipidation machinery which is essential for their integration into autophagy-related and unrelated membranes [ 53 ]. The effect of GABARAP subfamily protein lipidation on cell surface protein trafficking will be interesting to determine in future studies.…”

Section: Discussionmentioning

confidence: 99%

Lack of GABARAP-Type Proteins Is Accompanied by Altered Golgi Morphology and Surfaceome Composition

Sanwald

Dobner

Simons

et al. 2020

IJMS

View full text Add to dashboard Cite

GABARAP (γ-aminobutyric acid type A receptor-associated protein) and its paralogues GABARAPL1 and GABARAPL2 comprise a subfamily of autophagy-related Atg8 proteins. They are studied extensively regarding their roles during autophagy. Originally, however, especially GABARAPL2 was discovered to be involved in intra-Golgi transport and homotypic fusion of post-mitotic Golgi fragments. Recently, a broader function of mammalian Atg8s on membrane trafficking through interaction with various soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNAREs) was suggested. By immunostaining and microscopic analysis of the Golgi network, we demonstrate the importance of the presence of individual GABARAP-type proteins on Golgi morphology. Furthermore, triple knockout (TKO) cells lacking the whole GABARAP subfamily showed impaired Golgi-dependent vesicular trafficking as assessed by imaging of fluorescently labelled ceramide. With the Golgi apparatus being central within the secretory pathway, we sought to investigate the role of the GABARAP-type proteins for cell surface protein trafficking. By analysing the surfaceome composition of TKOs, we identified a subset of cell surface proteins with altered plasma membrane localisation. Taken together, we provide novel insights into an underrated aspect of autophagy-independent functions of the GABARAP subfamily and recommend considering the potential impact of GABARAP subfamily proteins on a plethora of processes during experimental analysis of GABARAP-deficient cells not only in the autophagic context.

show abstract

“…First, mitochondria are a source for phagophore membranes during autophagosome biogenesis ( Hailey et al, 2010 ). Second, mitochondria also provide phospholipids, like phosphatidylethanolamine (PE), which gets covalently linked to LC3 by ATG3 and ATG7 during autophagy initiation to form the active, lipidated LC3-II conjugate ( Hsu and Shi, 2017 ; Martens and Fracchiolla, 2020 ). LC3 family proteins can also interact with the mitochondria-specific lipid cardiolipin, which can act as a biosensor for oxidative damage and an autophagic degradation signal when it translocates to the outer mitochondrial membrane ( Antón et al, 2016 ).…”

Section: The Crosstalk Between Mitochondria and Autophagymentioning

confidence: 99%

Targeting the Mitochondria-Proteostasis Axis to Delay Aging

Zimmermann

Madreiter‐Sokolowski

Stryeck

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Human life expectancy continues to grow globally, and so does the prevalence of age-related chronic diseases, causing a huge medical and economic burden on society. Effective therapeutic options for these disorders are scarce, and even if available, are typically limited to a single comorbidity in a multifaceted dysfunction that inevitably affects all organ systems. Thus, novel therapies that target fundamental processes of aging itself are desperately needed. In this article, we summarize current strategies that successfully delay aging and related diseases by targeting mitochondria and protein homeostasis. In particular, we focus on autophagy, as a fundamental proteostatic process that is intimately linked to mitochondrial quality control. We present genetic and pharmacological interventions that effectively extend health- and life-span by acting on specific mitochondrial and pro-autophagic molecular targets. In the end, we delve into the crosstalk between autophagy and mitochondria, in what we refer to as the mitochondria-proteostasis axis, and explore the prospect of targeting this crosstalk to harness maximal therapeutic potential of anti-aging interventions.

show abstract

Activation and targeting of ATG8 protein lipidation

Cited by 144 publications

References 180 publications

Progress and Challenges in the Use of MAP1LC3 as a Legitimate Marker for Measuring Dynamic Autophagy In Vivo

Progress and Challenges in the Use of MAP1LC3 as a Legitimate Marker for Measuring Dynamic Autophagy In Vivo

Lack of GABARAP-Type Proteins Is Accompanied by Altered Golgi Morphology and Surfaceome Composition

Targeting the Mitochondria-Proteostasis Axis to Delay Aging

Contact Info

Product

Resources

About