Volume 2 (2018)
Cover: This month in Cell Stress: Kinase signaling in the innate immune system. Fluorescence microscopic depiction of immune cell responses within the CNS upon chronic pain. Images by Centre for Nanoscale BioPhotonics (CNBP) licensed under the CC BY 2.0 license. Image modified by Cell Stress. The cover is published under the CC BY 4.0 license.
Mitochondrial stress management: a dynamic journey
Miriam Valera-Alberni1,2 and Carles Canto1
Mitochondria undergo continuous challenges in the course of their life, from their generation to their degradation. These challenges include the management of reactive oxygen species, the proper assembly of mitochondrial respiratory complexes and the need to balance potential mutations in the mitochondrial DNA. The detection of damage and the ability to keep it under control is critical to fine-tune mitochondrial function to the organismal energy needs. In this review, we will analyze the multiple mechanisms that safeguard mitochondrial function in light of in crescendo damage. This sequence of events will include initial defense against excessive reactive oxygen species production, compensation mechanisms by the unfolded protein response (UPRmt), mitochondrial dynamics and elimination by mitophagy.
Therapeutic anti-tumor immunity directed against neo-epitopes by intratumor delivery of mRNA encoding MLKL
Lien Van Hoecke1,2 and Xavier Saelens1,2,3
We have developed a potentially generic treatment method to induce tumor antigen-specific cellular immunity based on the transient intra-tumor expression of the necroptosis-inducing factor MLKL (Figure 1). Importantly, we have
Base editors: a powerful tool for generating animal models of human diseases
Zongyang Lu1,2 and Xingxu Huang1,3
BASE EDITORS: A NOVEL GENOME ENGINEERING TOOL Genetically engineered mouse models of human diseases have long been used in understanding the underlying mechanisms of the clinically relevant genetic disorders. In
Unweaving the role of nuclear Lamins in neural circuit integrity
Samantha L. Deal1 and Shinya Yamamoto1,2,3,4
Structural integrity of the nuclear membrane is essential for the homeostasis of eukaryotic cells. Critical components of this process are Lamins or type-V intermediate filament proteins that form a meshwork
Red blood cell extracellular vesicles as robust carriers of RNA-based therapeutics
Chanh Tin Pham1, Xin Zhang1, Austin Lam1, Minh TN Le1
The emerging RNA-based therapeutics are renowned for a wide array of druggable targets, which are difficult to achieve by conventional therapies, with high specificity and great versatility. RNA-based drugs function
New insights into the role of soluble E-cadherin in tumor angiogenesis
Maggie K.S. Tang1, Philip P. Ip2 and Alice S.T. Wong1
Ovarian cancer, the leading cause of death among all gynecological malignancies, is a highly aggressive disease with a propensity for metastasis. Due to the discreet anatomical location, by the time
Neuronal Lamin regulates motor circuit integrity and controls motor function and lifespan
Lisa J. Oyston1,2,3, Yong Qi Lin1, Thang M. Khuong1, Qiao-Ping Wang1, Man Tat Lau1, Teleri Clark1 and G. Gregory Neely1
Neuronal aging involves a progressive decline in cognitive abilities and loss of motor function. Mutations in human Lamin genes (LMNA, LMNB1, LMNB2) lead to a wide-range of diseases including muscular dystrophy, peripheral neuropathy and progeria. Here we investigate the role of neuronal Lamin in regulating age-related phenotypes. Neuronal targeting of Lamin led to shortened lifespan, progressive impairment of motor function and loss of dopaminergic (DA) neurons within the protocerebral anterior medial (PAM) cluster in the Drosophila melanogaster brain. Loss of neuronal Lamin caused an age-related decline in neural physiology, with slower neurotransmission and increased chance of motor circuit failure with age. Unexpectedly, Lamin-dependent decline in motor function was specific for the chemical synapses of the dorsal longitudinal muscle (DLM). Together (...)
Oxidation of p62 as an evolutionary adaptation to promote autophagy in stress conditions
Elsje G. Otten1,§, Rhoda Stefanatos1, Bernadette Carroll1, Viktor I. Korolchuk1
Autophagy (literally meaning self-eating) is an intracellular trafficking pathway. It involves the formation of a double membraned organelle (called the autophagosome) around components of the cell, such as damaged proteins,
How to use a multipurpose SNARE: The emerging role of Snap29 in cellular health
Valeria Mastrodonato1,#, Elena Morelli1,# and Thomas Vaccari1
[table id=90 /] INTRODUCTION The specialized trafficking routes that evolved between compartments of the endomembrane system rely on a wide set of proteins, including primarily SNAREs, Rab GTPases and a
Assay for high-throughput screening of inhibitors of the ASC-PYD inflammasome core filament
Lorenzo Sborgi1, Johanna Ude1, Mathias S. Dick1, Jonathan Vesin2, Marc Chambon2, Gerardo Turcatti2, Petr Broz1, Sebastian Hiller1
The protein ASC is a central component of most inflammasome complexes, forming functional oligomeric filaments that activate large amounts of pro-caspase-1 for further IL-1β processing and the induction of Gasdermin D-dependent cell death. The central role of inflammasomes in the innate immune response pose them as new molecular targets for therapy of diverse acute, chronic and inherited autoinflammatory pathologies. In recent years, an increasing number of molecules were proposed to modulate inflammasome signalling by interacting with different components of inflammasome complexes. However, the difficult in vitro reconstitution of the inflammasome has limited the development of specific on-target biochemical assays for compound activity confirmation and for drug discovery in high throughput screening setups. Here we describe a homogeneous, pH (...)
Dram1 regulates DNA damage-induced alternative autophagy
Meruna Nagata1, Satoko Arakawa1, Hirofumi Yamaguchi1, Satoru Torii1, Hazuki Endo1, Masatsune Tsujioka1, Shinya Honda1, Yuya Nishida1, Akimitsu Konishi1,2, Shigeomi Shimizu1
Autophagy is an evolutionarily conserved process that degrades subcellular constituents. Mammalian cells undergo two types of autophagy; Atg5-dependent conventional autophagy and Atg5-independent alternative autophagy, and the molecules required for the latter type of autophagy are largely unknown. In this study, we analyzed the molecular mechanisms of genotoxic stress-induced alternative autophagy, and identified the essential role of p53 and damage-regulated autophagy modulator (Dram1). Dram1 was sufficient to induce alternative autophagy. In the mechanism of alternative autophagy, Dram1 functions in the closure of isolation membranes downstream of p53. These findings indicate that Dram1 plays a pivotal role in genotoxic stress-induced alternative autophagy.
Therapeutic potential of DNA methyltransferase inhibitors with immune checkpoint inhibitor therapy in breast cancer
Na Luo1, Ayaka Sugiura2 and Justin M. Balko1,3,4,5
Tumor infiltrating lymphocytes (TILs) are a positive prognostic biomarker in breast cancer, particularly in hormone receptor-negative disease. High TILs associate with an improved survival rate in breast cancer patients, and
Therapeutic anti-tumor immunity directed against neo-epitopes by intratumor delivery of mRNA encoding MLKL
Lien Van Hoecke1,2 and Xavier Saelens1,2,3
We have developed a potentially generic treatment method to induce tumor antigen-specific cellular immunity based on the transient intra-tumor expression of the necroptosis-inducing factor MLKL (Figure 1). Importantly, we have
Red blood cell extracellular vesicles as robust carriers of RNA-based therapeutics
Chanh Tin Pham1, Xin Zhang1, Austin Lam1, Minh TN Le1
The emerging RNA-based therapeutics are renowned for a wide array of druggable targets, which are difficult to achieve by conventional therapies, with high specificity and great versatility. RNA-based drugs function
New insights into the role of soluble E-cadherin in tumor angiogenesis
Maggie K.S. Tang1, Philip P. Ip2 and Alice S.T. Wong1
Ovarian cancer, the leading cause of death among all gynecological malignancies, is a highly aggressive disease with a propensity for metastasis. Due to the discreet anatomical location, by the time
SKP2 and OTUD1 govern non-proteolytic ubiquitination of YAP that promotes YAP nuclear localization and activity
Fan Yao1, Zhenna Xiao1,2, Yutong Sun3 and Li Ma1,2
YAP and its paralog TAZ are key effectors of the evolutionarily conserved Hippo signaling pathway, a pathway that regulates organ size, tissue homeostasis, and tumorigenesis. In human cells, MST1/2 (mammalian
T lymphocytes against solid malignancies: winning ways to defeat tumours
Ignazio Caruana1,§, Luca Simula1,2,§, Franco Locatelli1,# and Silvia Campello2,3, #
INTRODUCTION When a tumour mass starts growing in the body, T lymphocytes are activated inside secondary lymphoid organs (SLOs) and mount an immune response against immuno-stimulating tumour antigens presented by
GFI1’s role in DNA repair suggests implications for tumour cell response to treatment
Charles Vadnais1 and Tarik Möröy1,2,3
GFI1 was discovered over 20 years ago and a large body of experimental evidence defines its function as a DNA binding transcriptional repressor. Since GFI1 does not possess any enzymatic
Mitochondrial dysfunction and its role in tissue-specific cellular stress
David Pacheu-Grau1, Robert Rucktäschel1 and Markus Deckers1
Mitochondrial bioenergetics require the coordination of two different and independent genomes. Mutations in either genome will affect mitochondrial functionality and produce different sources of cellular stress. Depending on the kind of defect and stress, different tissues and organs will be affected, leading to diverse pathological conditions. There is no curative therapy for mitochondrial diseases, nevertheless, there are strategies described that fight the various stress forms caused by the malfunctioning organelles. Here, we will revise the main kinds of stress generated by mutations in mitochondrial genes and outline several ways of fighting this stress.
Base editors: a powerful tool for generating animal models of human diseases
Zongyang Lu1,2 and Xingxu Huang1,3
BASE EDITORS: A NOVEL GENOME ENGINEERING TOOL Genetically engineered mouse models of human diseases have long been used in understanding the underlying mechanisms of the clinically relevant genetic disorders. In
Unweaving the role of nuclear Lamins in neural circuit integrity
Samantha L. Deal1 and Shinya Yamamoto1,2,3,4
Structural integrity of the nuclear membrane is essential for the homeostasis of eukaryotic cells. Critical components of this process are Lamins or type-V intermediate filament proteins that form a meshwork
Alzheimer’s disease: amyloid-based pathogenesis and potential therapies
Yixiu Zhou1, Yuhui Sun2, Quan-Hong Ma2 and Yaobo Liu2
INTRODUCTION Alzheimer’s disease (AD) is one of the most prevalent forms of dementia; in 2015, for example, AD affected ~46.8 million people worldwide. It is estimated that this number will
Membrane closure in stress induced-autophagosome formation
Eiji Morita1
Autophagy (macroautophagy) is a bulk degradation system that sequesters cytoplasmic components by generating double-layered isolation membranes and delivering these isolated contents to the lysosomes [cite]10.1146/annurev-cellbio-092910-154005[/cite]. Though this pathway was originally
Centriolar satellites prevent uncontrolled degradation of centrosome proteins: a speculative review
Nicolas Lecland1 and Andreas Merdes1
INTRODUCTION Centrosomes are cytoplasmic structures that serve as primary microtubule organizing centers in a large variety of animal cells. They consist of a pair of cylindrically shaped centrioles, surrounded by
Novel role of the SIRT4-OPA1 axis in mitochondrial quality control
Alexander Lang1 and Roland P. Piekorz1
Aging is defined by various molecular and cellular hallmarks, among them stem cell exhaustion, genomic instability, altered proteostasis, cellular senescence, and mitochondrial dysfunction [cite]10.1016/j.cell.2013.05.039[/cite]. Mitochondrial defects are considered major drivers