Review
Biochemistry & Molecular Biology
Yuxiang J. Huang, Daniel J. Klionsky
Summary: Mitophagy is a selective type of autophagy that removes superfluous or damaged mitochondria by engulfing them in a double-membrane structure called a mitophagosome. Recent research has focused on the molecular mechanisms and regulation of yeast mitophagy.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Editorial Material
Cell Biology
Yalan Wang, Hongyan Wang, Chenji Wang
Summary: In neuronal ceroid lipofuscinoses (NCLs), mutations in the KCTD7 gene lead to lysosomal dysfunction and macroautophagic/autophagic defects, resulting in the accumulation of lysosomal storage deposits. Our study demonstrates that KCTD7 is a key player in maintaining lysosomal and autophagic homeostasis, and it is biochemically linked with CLN5, another NCL causative gene, in a common neurodegenerative pathway.
Article
Cell Biology
Hyo Jeong Kim, Sun-Yong Kim, Dae-Ho Kim, Joon Seong Park, Seong Hyun Jeong, Young Won Choi, Chul-Ho Kim
Summary: This study reveals the degradation mechanism of AKT protein through ubiquitination and arginylation in cells, which is critical for cancer treatment. Modulating non-proteasomal proteolysis mechanisms like MUL1-mediated AKT ubiquitination may offer a novel therapeutic approach for cancer treatment.
Article
Cell Biology
Ying Yang, Damian Gatica, Xu Liu, Runliu Wu, Rui Kang, Daolin Tang, Daniel J. Klionsky
Summary: This study reports the role of uORF-mediated translational control in regulating multiple Atg proteins in yeast and human cells. These findings suggest that uORF-mediated translational control is a widely used mechanism among ATG genes and provide a model for how some ATG genes bypass translational suppression under stress conditions to maintain proper autophagy levels.
Review
Biochemistry & Molecular Biology
Yasuyoshi Sakai, Masahide Oku
Summary: The discovery of microautophagy dates back to 1966, and since then research has focused on understanding its physiological significance and molecular mechanisms. Recent studies have found that ATG proteins and ESCRT proteins play important roles in microautophagy.
Review
Biochemistry & Molecular Biology
Naveed Ur Rehman, Peichun Zeng, Zulong Mo, Shaoying Guo, Yunfeng Liu, Yifeng Huang, Qingjun Xie
Summary: Autophagy is a highly conserved degradation mechanism, but the autophagy mechanisms in response to different stressors in plants and animals remain unknown. Selective autophagy receptors (SARs) play important roles in executing specific biological processes.
Letter
Biochemistry & Molecular Biology
Oren Shatz, Zvulun Elazar
Summary: Autophagy is a cellular process that selectively eliminates cytoplasmic constituents through engulfment in an isolation membrane, or non-selectively recycles bulk cytoplasm. Autophagosome formation involves the elongation of a newly-formed membrane, called the phagophore, by direct lipid flow from a donor membrane. Recent research has made significant advancements in understanding the regulation of autophagy and autophagosome formation by different lipid species and associated protein complexes. This schematic summary provides an overview of the current understanding of autophagy and autophagosome biogenesis.
Review
Biochemistry & Molecular Biology
Jing Liu, Lijuan Wang, Hua He, Yueying Liu, Yiqun Jiang, Jinfeng Yang
Summary: Chaperone-mediated autophagy (CMA) is a process that degrades proteins labeled with KFERQ-like motifs within cells to terminate their functioning. CMA plays a crucial role in cell proliferation and apoptosis. Its relationship with cancer is complex, with contradictory effects in cancer cells and untransformed cells, leading to interest in regulating CMA activity for cancer therapy.
Article
Cell Biology
Zhihua Zheng, Man Zhao, Hao Shan, Dongmei Fang, Zuyi Jin, Jiuge Tang, Zhiping Liu, Liang Hong, Peiqing Liu, Min Li
Summary: In this study, the researchers found that STING1 activation can induce both canonical and non-canonical autophagy. They also discovered that STING1-induced NCA is an efficient antiviral pathway that can effectively inhibit DNA virus HSV-1.
Article
Cell Biology
Damian Gatica, Xin Wen, Heesun Cheong, Daniel J. Klionsky
Summary: Macroautophagy/autophagy is a crucial catabolic process involving the sequestration and degradation of cellular components within autophagosomes. The vacuolar membrane protein Vac8 plays a key role in anchoring the PAS to the vacuolar membrane, facilitating efficient autophagy. Proper localization of the Atg1 initiation complex is essential for robust autophagy activity.
Article
Cell Biology
Yuxiang J. Huang, Daniel J. Klionsky
Summary: Research has found that Atg11 plays different roles in selective macroautophagy/autophagy between yeast and mammals, suggesting that it may have gained additional functions in evolution.
Article
Biochemistry & Molecular Biology
Mikhail Rudinskiy, Maurizio Molinari
Summary: Conserved catabolic pathways operate to remove aberrant polypeptides from the endoplasmic reticulum (ER), utilizing ERAD pathways and ER-phagy. ERAD pathways control retrotranslocation of misfolded proteins across the ER membrane, while ER-phagy segregates proteins into ER subdomains that eventually vesiculate. These ER-derived vesicles can be captured by autophagosomes, endolysosomes/vacuoles, or fused with degradative organelles.
Article
Chemistry, Medicinal
Yue Zhong, Fanglian Chi, Hanyu Wu, Yunxiao Liu, Zhancheng Xie, Wenlong Huang, Wei Shi, Hai Qian
Summary: Targeted protein degradation technology represents a new therapeutic modality in drug discovery. Researchers are exploring optimized protein degraders to overcome the limitations of classical PROTACs and achieve more precise protein degradation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Aifang Cheng, Kai-Hei Tse, Hei-Man Chow, Yunqiao Gan, Xuan Song, Fulin Ma, Yi Xuan Yvonne Qian, Weiyi She, Karl Herrup
Summary: ATM protein is associated with cellular organelles such as synaptic vesicles, endosomes, and lysosomes, with its deficiency impacting autophagy and lysosomal function in neurons. This disruption leads to impaired neuronal functions including synaptic maintenance, neuronal survival, and glucose uptake.
Article
Microbiology
Minghui Li, Ping Yan, Xia Shen, Zhenni Liu, Quanxi Wang, Yifan Huang, Yijian Wu
Summary: MDRV infection induces autophagy in DF-1 cells, promotes fusion of autophagosomes and lysosomes, inhibits autophagolysosome degradation, and enhances virus replication.
VETERINARY MICROBIOLOGY
(2021)
Article
Cell Biology
Zhangyuan Yin, Zhihai Zhang, Yuchen Lei, Daniel J. Klionsky
Summary: This study reveals that the Ccr4-Not complex in Saccharomyces cerevisiae has bidirectional roles in regulating autophagy before and after nutrient deprivation. Under nutrient-rich conditions, Ccr4-Not promotes the degradation of certain ATG genes to maintain basal autophagy. However, upon starvation, Ccr4-Not switches its role to promote the expression of a different subset of ATG genes, which is required for sufficient autophagy induction and activity.
Editorial Material
Cell Biology
Fangyang Wang, Ying Yang, Daniel J. Klionsky, Sami N. Malek
Summary: The discovery of recurrent gene mutations in chaperones or components of V-ATPase in FL has raised new insights into the biology of this disease. Mutations in ATP6V1B2 and VMA21 impair lysosomal V-ATPase activity, leading to elevated lysosomal pH and increased autophagic flux, which is crucial for the survival of FL cells. Targeting autophagy alone or in combination with other therapies could be a promising therapeutic strategy for FL patients.
Article
Cell Biology
Ying Yang, Damian Gatica, Xu Liu, Runliu Wu, Rui Kang, Daolin Tang, Daniel J. Klionsky
Summary: This study reports the role of uORF-mediated translational control in regulating multiple Atg proteins in yeast and human cells. These findings suggest that uORF-mediated translational control is a widely used mechanism among ATG genes and provide a model for how some ATG genes bypass translational suppression under stress conditions to maintain proper autophagy levels.
Review
Cell Biology
Kai Kaarniranta, Janusz Blasiak, Paloma Liton, Michael Boulton, Daniel J. Klionsky, Debasish Sinha
Summary: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the aging population. The progression of AMD is characterized by atrophic alterations in the retinal pigment epithelium and the formation of lipofuscin and deposits. Chronic oxidative stress, protein aggregation, and inflammation may contribute to the development of AMD.
Article
Cell Biology
Xin Chen, Xinxin Song, Jingbo Li, Ruoxi Zhang, Chunhua Yu, Zhuan Zhou, Jiao Liu, Siyan Liao, Daniel J. Klionsky, Guido Kroemer, Jinbao Liu, Daolin Tang, Rui Kang
Summary: This study identifies HPCAL1 as a novel autophagy receptor for the selective degradation of CDH2 during ferroptosis. Depletion of CDH2 increases susceptibility to ferroptotic death. The phosphorylation of HPCAL1 and the non-classical LC3-interacting region motif play key roles in the autophagic degradation of CDH2. A ferroptosis inhibitor is found to suppress HPCAL1 expression. Inhibition of HPCAL1 prevents ferroptosis-induced tumor suppression and pancreatitis in mouse models.
Review
Cell Biology
Zi-Fang Shen, Lin Li, Xue-Ming Zhu, Xiao-Hong Liu, Daniel J. Klionsky, Fu-Cheng Lin
Summary: Mitophagy, an important cellular process, is critical for maintaining mitochondrial quality control. While its role has been well-studied in mammalian cells and certain model organisms, the significance of mitophagy in fungi, especially pathogenic filamentous fungi, is still in its early stages. Recent studies have found that mitophagy plays a vital role in spore production, vegetative growth, and virulence of pathogenic fungi.
Review
Cell Biology
Yangchun Xie, Rui Kang, Daniel J. Klionsky, Daolin Tang
Summary: Selenoprotein GPX4 is the main oxidoreductase that uses glutathione to scavenge lipid peroxidation products. It has three isoforms with distinct expression patterns and its loss can trigger various forms of cell death and inflammation. GPX4's interaction with autophagy pathway modulates cell fate in response to oxidative stress. Impairment of GPX4 function is implicated in various diseases. Furthermore, a specific mutation in GPX4 is associated with a rare and fatal disease in newborns. This article discusses the roles of GPX4 in cell death, autophagy, and disease.
Article
Cell Biology
Prakash P. Praharaj, Srimanta Patra, Soumya R. Mishra, Subhadip Mukhopadhyay, Daniel J. Klionsky, Shankargouda Patil, Sujit K. Bhutia
Summary: This study found that cisplatin treatment activated higher mitophagy in oral cancer stem cells by regulating CLU levels. CLU regulated mitochondrial fission by activating AKT kinase, leading to mitochondrial fission. Furthermore, CLU-mediated mitophagy positively regulated oral cancer stem cells by degrading MSX2 and preventing its nuclear translocation, which suppressed SOX2 activity and inhibited cancer stemness and self-renewal ability.
Editorial Material
Cell Biology
Ying Yang, Daniel J. J. Klionsky
Summary: TNF is an important cytokine that regulates immune responses to microbial infection. It can induce activation of NFKB/NF-kappa B or cell death through the formation of TNFRSF1A/TNFR1 complexes. Abnormal TNF-induced cell death is associated with human inflammatory diseases, and protective cell death checkpoints are crucial in preventing TNF cytotoxicity.
Editorial Material
Cell Biology
Yashveer Chohan, Emily A. Eitzman, Wayne D. Hawkins, Daniel J. Klionsky
Summary: A recent study has found that the recruitment of Egfr to synapses suppresses autophagic degradation of presynaptic proteins, which is necessary for proper neuronal circuit development. Inactivation of Egfr during late development leads to increased levels of autophagy in the brain and decreased neuronal circuit development. The presence of brp in the synapse is critical for proper neuronal functioning, and increased autophagy due to Egfr inactivation results in decreased brp levels and reduced neuronal connectivity.
Review
Cell Biology
Qian Xue, Rui Kang, Daniel J. Klionsky, Daolin Tang, Jinbao Liu, Xin Chen
Summary: Copper is an essential trace element that regulates enzymes and transcription factors, but high concentrations can lead to cell death and autophagy. Abnormal copper metabolism is associated with various diseases, including Wilson disease and cancer, and copper-based compounds have potential therapeutic applications. Understanding copper metabolic processes may enhance cancer diagnosis and treatment.
Review
Biochemistry & Molecular Biology
Yuchen Lei, Daniel. J. J. Klionsky
Summary: Macroautophagy/autophagy is a crucial catabolic pathway involved in maintaining cell homeostasis and promoting cell survival. Dysregulation of autophagy is linked to various human diseases, necessitating precise regulation at multiple levels to prevent inappropriate activity. This review focuses on the transcriptional regulation of autophagy, summarizing the transcription factors that control autophagy gene expression in yeast and mammalian cells. The association between changes in transcriptional regulation of autophagy and human pathophysiologies are also discussed.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Multidisciplinary Sciences
Manuel Lauinger, Daniel Christen, Rhena F. U. Klar, Carole Roubaty, Christoph E. Heilig, Michael Stumpe, Jennifer J. Knox, Nikolina Radulovich, Laura Tamblyn, Irene Y. Xie, Peter Horak, Andrea Forschner, Michael Bitzer, Uwe A. Wittel, Melanie Boerries, Claudia R. Ball, Christoph Heining, Hanno Glimm, Martina Froehlich, Daniel Huebschmann, Steven Gallinger, Ralph Fritsch, Stefan Froehling, Grainne M. O'Kane, Joern Dengjel, Tilman Brummer
Summary: This study functionally characterizes BRAF exon 12 deletions and compares them with other BRAF ss 3-alpha C mutants. It demonstrates that BRAF(Delta ss 3-alpha C) deletion mutants form stable dimers and multiprotein complexes, and their dimerization is necessary. Some mutants with aromatic amino acid insertions at the deletion junction exhibit resistance to monomer-favoring RAF inhibitors while being sensitive to dimer-favoring inhibitors.
Article
Biology
Panagiota Kolitsida, Vladimir Nolic, Jianwen Zhou, Michael Stumpe, Natalie M. Niemi, Jorn Dengjel, Hagai Abeliovich
Summary: The mitophagic degradation of mitochondrial matrix proteins in Saccharomyces cerevisiae is selectively regulated by the matrix kinases Pkp1 and Pkp2, which are in turn regulated by the phosphatase Aup1/Ptc6. These proteins also regulate the phosphorylation status and catalytic activity of the pyruvate dehydrogenase complex, which is critical for mitochondrial metabolism. The pyruvate dehydrogenase complex has been found to have a novel function in regulating mitophagic selectivity independent of its enzymatic activity.
LIFE SCIENCE ALLIANCE
(2023)
Article
Immunology
Masoumeh Azimirad, Maryam Noori, Sahar Amirkamali, Gelareh Nasiri, Hamid Asadzadeh Aghdaei, Abbas Yadegar, Daniel J. Klionsky, Mohammad Reza Zali
Summary: This study reveals that C. difficile bacteria can induce autophagy through both toxin-dependent and independent mechanisms, suggesting the potential role of other C. difficile virulence factors in autophagy modulation.
MICROBIAL PATHOGENESIS
(2023)
