TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy

Wu, Wenxian; Wang, Xiaojing; Sun, Yan; Berleth, Niklas; Deitersen, Jana; Schlütermann, David; Stuhldreier, Fabian; Wallot-Hieke, Nora; Mendiburo, María José; Cox, Jan; Peter, Christoph; Bergmann, Ann Kathrin; Stork, Björn

doi:10.1080/15548627.2021.1899667

Cited by 60 publications

(43 citation statements)

References 80 publications

(134 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both Yersinia and Listeria have been shown to activate autophagic mechanisms, and it was suggested that those mechanisms facilitate the destruction of the bacteria [44,45]. Activation of MLKL was also reported to facilitate autophagy [46]. It, therefore, seems plausible that the lysosomal destruction of intracellular bacteria that we found to be induced by ubiquitinated MLKL is exerted via enhancement of autophagy.…”

Section: Mlkl Ubiquitination Also Facilitates the Destruction Of Some Other Intracellular Bacteriasupporting

confidence: 51%

Site-specific ubiquitination of MLKL targets it to endosomes and targets Listeria and Yersinia to the lysosomes

2022

View full text Add to dashboard Cite

Phosphorylation of the pseudokinase mixed lineage kinase domain-like protein (MLKL) by the protein kinase RIPK3 targets MLKL to the cell membrane, where it triggers necroptotic cell death. We report that conjugation of K63-linked polyubiquitin chains to distinct lysine residues in the N-terminal HeLo domain of phosphorylated MLKL (facilitated by the ubiquitin ligase ITCH that binds MLKL via a WW domain) targets MLKL instead to endosomes. This results in the release of phosphorylated MLKL within extracellular vesicles. It also prompts enhanced endosomal trafficking of intracellular bacteria such as Listeria monocytogenes and Yersinia enterocolitica to the lysosomes, resulting in decreased bacterial yield. Thus, MLKL can be directed by specific covalent modifications to differing subcellular sites, whence it signals either for cell death or for non-deadly defense mechanisms.

show abstract

Section: Mlkl Ubiquitination Also Facilitates the Destruction Of Some Other Intracellular Bacteriasupporting

confidence: 51%

Site-specific ubiquitination of MLKL targets it to endosomes and targets Listeria and Yersinia to the lysosomes

2022

View full text Add to dashboard Cite

show abstract

“…RIPK3, a necroptosis-regulating kinase, has been found to be closely associated with lysosomal biogenesis ( 41 , 42 ). In TNF-treated murine L929 fibroblasts, RIPK3 promoted necroptosis by blocking lysosomal degradation of autophagosomes ( 43 ). In septic acute kidney injury, upregulated RIPK3 contributes to lysosomal dysfunction and the accumulation of autophagosomes in renal proximal tubular epithelial cells ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Receptor-Interacting Protein Kinase 3 Suppresses Mitophagy Activation via the Yes-Associated Protein/Transcription Factor EB Pathways in Septic Cardiomyopathy

Zhu

Chen

Wang

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Mitophagy, known as the main mechanism of mitochondrial quality control, determines the pathophysiology of septic cardiomyopathy, although the precise regulatory mechanisms remain elusive. Data from the present study suggested that receptor-interacting protein kinase 3 (RIPK3) expression could be enhanced in response to lipopolysaccharide (LPS) challenge. Upregulated RIPK3 expression was accompanied by severe cardiac injury and cardiac dysfunction. Further examination revealed that elevated RIPK3 expression subsequently inhibited the Yes-associated protein (YAP) pathway, which was accompanied by reduced transcription factor EB (TFEB) expression. Inhibition of TFEB would reduce mitophagy, which ultimately induced cardiomyocyte death under LPS challenge. In contrast, loss of RIPK3 induced the YAP/TFEB/mitophagy pathway alleviated the sensitivity of cardiomyocytes to LPS-induced cytotoxicity. Collectively, the RIPK3/YAP/TFEB axis was confirmed to be responsible for the pathogenesis of septic cardiomyopathy by inhibiting mitophagy. These findings have potential significance for the progression of new approaches to the treatment of septic cardiomyopathy.

show abstract

“…Conversely to the well-regulated and cytoprotective mechanism of autophagy, necroptosis constitutes an inflammatory form of cell death, leading to tissue necrosis [ 98 , 99 ]. Necroptosis is mainly mediated by death receptors like TNFRSF1A/TNFR1 (TNF receptor superfamily member 1A), although there are other pathways leading to necroptosis as well [ 100 ].…”

Section: The Link Between Endoplasmic Reticulum (Er) Stress Oxidative...mentioning

confidence: 99%

“…Necroptosis as well as autophagy are mechanisms balancing cell death and survival, and a crosstalk between these two mechanisms has been reported [ 98 ]. Wu et al demonstrated the link between autophagy and necroptosis, since RIPK3 connects directly with AMPK, phosphorylating its catalytic subunit PRKAA1/2 at T183/T172.…”

Section: The Link Between Endoplasmic Reticulum (Er) Stress Oxidative...mentioning

confidence: 99%

“…After activation, AMPK phosphorylates the autophagy-mediating proteins ULK1 and BECN1. Moreover, Wu et al could show that the lysosomal decomposition of autophagosomes is inhibited by TNF-induced necroptosis [ 98 ]. Therefore, RIPK3 and AMPK-activating kinases constitute a link between kinases regulating autophagy, and kinases regulating necroptosis.…”

Section: The Link Between Endoplasmic Reticulum (Er) Stress Oxidative...mentioning

confidence: 99%

See 1 more Smart Citation

Autophagy, Oxidative Stress and Cancer Development

Taucher

Mykoliuk

Fediuk

et al. 2022

Cancers

View full text Add to dashboard Cite

Autophagy is an important cellular repair mechanism, aiming at sequestering misfolded and dysfunctional proteins and damaged cell organelles. Dysfunctions in the autophagy process have been linked to several diseases, like infectious and neurodegenerative diseases, type II diabetes mellitus and cancer. Living organisms are constantly subjected to some degree of oxidative stress, mainly induced by reactive oxygen and nitrogen species. It has been shown that autophagy is readily induced by reactive oxygen species (ROS) upon nutrient deprivation. In recent years, research has increasingly focused on outlining novel therapeutic targets related to the autophagy process. With this review of the literature, we want to give an overview about the link between autophagy, oxidative stress and carcinogenesis.

show abstract

TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy

Abstract: Stork (2021): TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy, Autophagy,

Cited by 60 publications

References 80 publications

Site-specific ubiquitination of MLKL targets it to endosomes and targets Listeria and Yersinia to the lysosomes

Site-specific ubiquitination of MLKL targets it to endosomes and targets Listeria and Yersinia to the lysosomes

Receptor-Interacting Protein Kinase 3 Suppresses Mitophagy Activation via the Yes-Associated Protein/Transcription Factor EB Pathways in Septic Cardiomyopathy

Autophagy, Oxidative Stress and Cancer Development

Contact Info

Product

Resources

About