MTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy

Ma, Xi; Zhang, Shen; He, Long; Rong, Yueguang; Brier, Livia W.; Sun, Qiming; Liu, Rong; Fan, Weiliang; Chen, She; Yue, Zhenyu; Kim, Joungmok; Guan, Kun Liang; Li, Defa; Zhong, Qing

doi:10.1080/15548627.2016.1269988

Cited by 73 publications

(83 citation statements)

References 46 publications

(93 reference statements)

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“…The other complex I-specific subunit, Atg38, helps to maintain the integrity of complex I [33]. NRBF2 is an apparent orthologue of budding yeast Atg38 in mammals, but its exact roles remain unresolved [34][35][36][37][38][39].…”

Section: Introductionmentioning

confidence: 99%

Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop to promote autophagy

Sun

Jiang

et al. 2020

Autophagy

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Macroautophagy (autophagy) is driven by the coordinated actions of core autophagy-related (Atg) proteins. Atg8, the core Atg protein generally considered acting most downstream, has recently been shown to interact with other core Atg proteins via their Atg8-family-interacting motifs (AIMs). However, the extent, functional consequence, and evolutionary conservation of such interactions remain inadequately understood. Here, we show that, in the fission yeast Schizosaccharomyces pombe, Atg38, a subunit of the phosphatidylinositol 3-kinase (PtdIns3K) complex I, interacts with Atg8 via an AIM, which is highly conserved in Atg38 proteins of fission yeast species, but not conserved in Atg38 proteins of other species. This interaction recruits Atg38 to Atg8 on the phagophore assembly site (PAS) and consequently enhances PAS accumulation of the PtdIns3K complex I and Atg proteins acting downstream of the PtdIns3K complex I, including Atg8. The disruption of the Atg38-Atg8 interaction leads to the reduction of autophagosome size and autophagic flux. Remarkably, the loss of this interaction can be compensated by an artificial Atg14-Atg8 interaction. Our findings demonstrate that the Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop between Atg8 and the PtdIns3K complex I to promote efficient autophagosome formation, underscore the prevalence and diversity of AIMmediated connections within the autophagic machinery, and reveal unforeseen flexibility of such connections.

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Section: Introductionmentioning

confidence: 99%

Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop to promote autophagy

Sun

Jiang

et al. 2020

Autophagy

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“…Dysfunction of autophagy has been implicated in a broad spectrum of human diseases including cancers, neurodegeneration, infectious diseases, metabolic diseases and aging [39]. Autophagy can be activated under stress conditions such as starvation, endoplasmic reticulum (ER) stress, and organelles damage and pathogen infection.…”

Section: Ros Induce Autophagymentioning

confidence: 99%

Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species

Farrar

et al. 2017

Cell Physiol Biochem

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Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, cells will produce numerous ROS, and the living organisms eventually evolve series of response mechanisms to adapt to the ROS exposure as well as utilize it as the signaling molecules. ROS molecules would trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy. Growing evidences have suggested that ROS play a critical role as the signaling molecules throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelles structure and bio-molecules, which lead to inflammatory response that is a known underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress, can transform toxic metabolites into ROS, such as superoxide anion, hydrogen peroxide and hydroxyl radical which might cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as the non-enzymatic antioxidants which collectively reduce oxidative state. Herein, we review the recent novel findings of cellular processes induced by ROS, and summarize the roles of cellular endogenous antioxidant systems as well as natural anti-oxidative compounds in several human diseases caused by ROS in order to illustrate the vital role of antioxidants in prevention against oxidative stress.

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“…NRBF2 is a regulator of autophagy, a cellular process for disassembly of dysfunctional cytosolic components . In its phosphorylated form, NRBF2 inhibits autophagy, while promoting it in its unphosphorylated form . Intact autophagy, in turn, was recently reported to confer protection against autoimmune disorders such as lupus nephritis .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus

Vordenbäumen

Brinks

Hoyer

et al. 2019

Arthritis & Rheumatology

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Objective. To investigate the role of epitope spreading in established systemic lupus erythematosus (SLE). Methods. IgG autoantibody reactivity with 398 distinct recombinant proteins was measured over a period of 6 years in 69 SLE patients and compared to that in 45 controls. Changes in mean fluorescence intensity (MFI), number of autoantibodies to distinct antigens, and reactivity with distinct clones of established antigenic targets (e.g., U1 RNP, Sm, and ribosomal P) representing epitope fine mapping were assessed. Linear mixed modeling, adjusted with Bonferroni correction for age and sex, was applied.Results. The total number of autoantibodies, mean MFI, and number of autoantibodies in epitope fine mapping were higher in SLE patients compared to controls (P < 0.0001). The total number of antibodies to distinct autoantigens remained stable over time, while the mean MFI decreased over time in SLE (P < 0.021). SLE patients showed variable recognition of epitopes in fine mapping over time. In particular, in SLE patients, more clones of the U1 RNP complex were recognized at the time of new organ involvement (+0.65) (P = 0.007). Mean MFI was higher in patients with lupus nephritis (P = 0.047). The time-averaged MFIs of 22 individual autoantibodies (including double-stranded DNA [dsDNA]) were higher, after Bonferroni correction, in SLE (P < 0.0001). The MFIs of dsDNA and histone cluster 2 H3c were associated with scores on the Systemic Lupus Activity Measure (P < 0.0001).Conclusion. Longitudinal surveillance of the IgG autoantibody repertoire in established SLE reveals evidence of sustained breadth of autoantibody repertoire without significant expansion. Associations of disease activity with dsDNA and with histone H3 autoantibodies were confirmed.

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MTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy

Cited by 73 publications

References 46 publications

Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop to promote autophagy

Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop to promote autophagy

Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species

Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus

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