Article
Virology
Ayan K. Ghosh, Yu-Pin Su, Michael Forman, Robert F. Keyes, Brian C. Smith, Xin Hu, Marc Ferrer, Ravit Arav-Boger
Summary: A compound called ARP101 induces the SQSTM1/p62-Keap1-Nrf2 pathway to suppress HCMV replication, providing a novel antiviral strategy for HCMV treatment.
JOURNAL OF VIROLOGY
(2023)
Review
Cell Biology
Baike Ning, Shuqi Hang, Wenhe Zhang, Caiwen Mao, Dan Li
Summary: There is a close connection between autophagy and antioxidant pathways, and identifying the bridging factors that regulate both can be beneficial for treating diseases related to autophagy dysfunction and oxidative stress.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Yanan Zhao, Jing Lu, Ankang Mao, Ranran Zhang, Shuang Guan
Summary: The study demonstrated that autophagy inhibition can protect cells against alcohol-induced ferroptosis by activating the p62-Keap1-Nrf2 pathway. Inhibition of autophagy resulted in the accumulation of p62, facilitating the translocation of Nrf2 into the nucleus and upregulating the expression of its target proteins.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Randong Yang, Shurong Ma, Ran Zhuo, Lingqi Xu, Siqi Jia, Pengcheng Yang, Ye Yao, Haibo Cao, Liya Ma, Jian Pan, Jian Wang
Summary: Autophagy has dual roles in cancer, and CYN, a natural compound, exhibits antitumor effects against NB by modulating autophagy to inhibit apoptosis. CYN may be a promising candidate for NB treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alessia Garufi, Eugenia Giorno, Maria Saveria Gilardini Montani, Giuseppa Pistritto, Alessandra Crispini, Mara Cirone, Gabriella D'Orazi
Summary: The study found that the zinc-curcumin compound can activate NRF2 and decrease the levels of Keap1, increasing cancer cell sensitivity to Zn(II)-curc-induced cell death. The crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to enhance cancer patient response to therapies.
Article
Plant Sciences
Weiwei Zhang, Xu Geng, Qing Dong, Xiuhan Li, Ping Ye, Mengyuan Lin, Bin Xu, Hong Jiang
Summary: This study investigated the mechanism of realgar-induced neurotoxicity and its effects on autophagy and the Keap1-Nrf2-ARE pathway. The results showed that arsenic from realgar accumulated in the brain and blood, leading to neuronal and synaptic damage, decreased exploratory behavior and spontaneous movement, and impaired memory ability in rats. The mechanism may involve realgar-mediated autophagy impairment and continuous activation of the Nrf2 pathway. However, the activation of the Nrf2 pathway was insufficient to counteract oxidative damage, resulting in aggravated apoptosis in the cerebral cortex.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Food Science & Technology
Fengge Wang, Miao Liu, Peng Lin, Jishui Wang, Lihua Zhang, Haiyan Zhang, Miaomiao Qu, Shuxiong Chen, Dongmei Man
Summary: Preeclampsia is a serious complication of pregnancy, with accumulation of trophoblastic reactive oxygen species and placental dysfunction as potential pathogenic bases. Astragaloside IV (AS IV), a major active component of Astragalus membranaceus, protects trophoblasts from oxidative stress-induced damage by activating the Nrf2-Keap1-p62 feedback loop.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Cell Biology
Yinfeng Xu, Yaosen Wu, Lei Wang, Zhuo Ren, Lijiang Song, Hui Zhang, Chuying Qian, Qian Wang, Zhengfu He, Wei Wan
Summary: The study uncovered a regulatory role of autophagy in RNA metabolism, showing that autophagy-deficient cells have higher levels of 47S precursor rRNA due to accumulation of SQSTM1. This accumulation potentiates MTORC1 signaling, leading to increased rRNA transcription from rDNA and promoting protein synthesis and cell proliferation.
Article
Biochemistry & Molecular Biology
Masaaki Komatsu
Summary: In this review, the author discusses the history of p62 research in relation to autophagy and provides an overview of the formation, degradation, and physiological functions of the p62 body, including efficient degradation of ubiquitinated proteins and involvement in antioxidant stress response.
Article
Multidisciplinary Sciences
Jee-Yun Park, Hee-Young Sohn, Young Ho Koh, Chulman Jo
Summary: Curcumin activates Nrf2 through phosphorylation of p62 at S351, with PKC delta playing a crucial role in this process.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Yuta Horie, Takafumi Suzuki, Jin Inoue, Tatsuro Iso, Geoffrey Wells, Terry W. Moore, Tsunehiro Mizushima, Albena T. Dinkova-Kostova, Takuma Kasai, Takashi Kamei, Seizo Koshiba, Masayuki Yamamoto
Summary: This study reveals that the dissociation of Keap1 from Nrf2, known as the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62-mediated Nrf2 activation, rather than by electrophilic Nrf2 inducers. Insights gained from this research can be used for the development of Nrf2 activators targeting the Keap1-Nrf2 interaction.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mara Cirone, Gabriella D'Orazi
Summary: Expanding the understanding of the molecular mechanisms in tumor development, especially the interaction between oncogenic pathways, may lead to improved personalized cancer therapies. Nuclear factor erythroid 2-related factor 2 (NRF2) is crucial in cancer progression, not only due to its antioxidant activity but also its cross-talk with several oncogenic pathways. Additionally, NRF2's involvement in gammaherpesvirus-driven carcinogenesis is intriguing, as these viruses utilize the NRF2 pathway to protect tumor cells and avoid excessive reactive oxygen species levels. Manipulating the NRF2 pathway at different stages of gammaherpesvirus-mediated carcinogenesis may have varying outcomes, making it a potential target for cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Xiaolan Fan, Tiantian Huang, Yingdong Tong, Ziqiang Fan, Ziyue Yang, Deying Yang, Xueping Mao, Mingyao Yang
Summary: p62, also known as SQSTM1, is a crucial predictor of autophagic flux and plays a role in maintaining protein homeostasis in cells. It has the ability to resist oxidative stress, and its multiple domains allow it to interact with vital signaling pathways, influencing cell proliferation, apoptosis, and survival. Recent studies have also shown its involvement in the aging process.
AGEING RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Yasukazu Takanezawa, Ryohei Harada, Yoshio Shibagaki, Yui Kashiwano, Ryosuke Nakamura, Yuka Ohshiro, Shimpei Uraguchi, Masako Kiyono
Summary: p62 interacts with NEDD4 to alleviate MeHg toxicity through the formation of a complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Plant Sciences
Yuan Meng, Rui Feng, Zhao Yang, Tingting Liu, Taoguang Huo, Hong Jiang
Summary: This study found that arsenic in realgar passes through the blood-brain barrier and accumulates in the brain, causing damage to neurons, synapses, and myelin sheaths in the cerebral cortex and a decrease in total antioxidant capacity. The specific mechanism involves the excessive activation of Nrf2 regulated by upstream signaling molecules ERK1/2 and p38 MAPK.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Junya Sango, Taichi Kakihana, Masahiko Takahashi, Yoshinori Katsuragi, Sergei Anisimov, Masaaki Komatsu, Masahiro Fujii
Summary: Nrf2 is an antioxidant transcriptional activator that plays a role in various human disorders. This study shows that the protein USP10 reduces dopamine-induced ROS production and apoptosis in neuronal cells by stimulating the antioxidant activity of Nrf2. USP10 is a key regulator of Nrf2 antioxidant activity in neuronal cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Masahiko Takahashi, Hiroki Kitaura, Akiyoshi Kakita, Taichi Kakihana, Yoshinori Katsuragi, Osamu Onodera, Yuriko Iwakura, Hiroyuki Nawa, Masaaki Komatsu, Masahiro Fujii
Summary: TDP-43 is a causative factor of ALS, and cytoplasmic TDP-43 aggregates are a characteristic pathology of the disease. USP10 promotes the clearance of TDP-43-positive stress granules (SGs), leading to the formation of TDP-43-positive aggregates. The interaction between TDP-35 and USP10 is RNA-binding-dependent, and impaired RNA binding of TDP-35 results in the formation of USP10-negative aggregates.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Neurosciences
Mai Sakai, Zhiqian Yu, Ryo Hirayama, Masa Nakasato, Yoshie Kikuchi, Chiaki Ono, Hiroshi Komatsu, Miharu Nakanishi, Hatsumi Yoshii, David Stellwagen, Tomoyuki Furuyashiki, Masaaki Komatsu, Hiroaki Tomita
Summary: This study explores the changes in autophagy signaling in the prefrontal cortex (PFC) under repeated social defeat (RSD) and their potential involvement in behavioral changes induced by stress. The results suggest that enhanced autophagy may alleviate stress-induced depression, and microglial autophagy plays a role in stress-induced behavioral changes.
Article
Biochemistry & Molecular Biology
Akiko Suzuki, Chihiro Iwaya, Kenichi Ogata, Hiroki Yoshioka, Junbo Shim, Isei Tanida, Masaaki Komatsu, Norihiro Tada, Junichi Iwata
Summary: Sjogren's syndrome is a chronic autoimmune disease characterized by immune cell infiltration of the exocrine glands. Deficiency in enzymes involved in the ubiquitin modification pathway leads to a Sjogren's syndrome-like phenotype, and activation of GATE16 is crucial for exocytosis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Letter
Gastroenterology & Hepatology
Wen-Xing Ding, Hong-Min Ni, Satoshi Waguri, Masaaki Komatsu
JOURNAL OF HEPATOLOGY
(2022)
Article
Cell Biology
Maiko Ono, Masaaki Komatsu, Bin Ji, Yuhei Takado, Masafumi Shimojo, Takeharu Minamihisamatsu, Eiji Warabi, Toru Yanagawa, Gen Matsumoto, Ichio Aoki, Nicholas M. Kanaan, Tetsuya Suhara, Naruhiko Sahara, Makoto Higuchi
Summary: In this study, evidence is provided that p62 exerts a protective role against neuronal death and neuroinflammation induced by abnormal tau accumulation. By eliminating neurotoxic tau species, p62 may act as a potential therapeutic target for the treatment of tauopathies.
Article
Cell Biology
Sang-Won Park, Pureum Jeon, Akinori Yamasaki, Hye Eun Lee, Haneul Choi, Ji Young Mun, Yong-Woo Jun, Ju-Hui Park, Seung-Hwan Lee, Soo-Kyeong Lee, You-Kyung Lee, Hyun Kyu Song, Michael Lazarou, Dong-Hyong Cho, Masaaki Komatsu, Nobuo N. Noda, Deok-Jin Jang, Jin-A Lee
Summary: This study identified the selective interactions of various membrane-anchored mATG8 proteins in mammals and developed tools to regulate the autophagy of disease-related protein aggregates. This has significant implications for understanding the functional roles of mATG8 proteins on autophagic membranes in autophagy research.
Correction
Cell Biology
Shuhei Nakamura, Saki Shigeyama, Satoshi Minami, Takayuki Shima, Shiori Akayama, Tomoki Matsuda, Alessandra Esposito, Gennaro Napolitano, Akiko Kuma, Tomoko Namba-Hamano, Jun Nakamura, Kenichi Yamamoto, Miwa Sasai, Ayaka Tokumura, Mika Miyamoto, Yukako Oe, Toshiharu Fujita, Seigo Terawaki, Atsushi Takahashi, Maho Hamasaki, Masahiro Yamamoto, Yukinori Okada, Masaaki Komatsu, Takeharu Nagai, Yoshitsugu Takabatake, Haoxing Xu, Yoshitaka Isaka, Andrea Ballabio, Tamotsu Yoshimori
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Masaaki Komatsu
Summary: In this review, the author discusses the history of p62 research in relation to autophagy and provides an overview of the formation, degradation, and physiological functions of the p62 body, including efficient degradation of ubiquitinated proteins and involvement in antioxidant stress response.
Editorial Material
Cell Biology
Reo Kurusu, Hideaki Morishita, Masaaki Komatsu
Summary: SQSTM1/p62 bodies are phase-separated condensates that play a crucial role in intracellular quality control and stress responses. A recent study discovered a novel substrate for selective autophagy called vault, which directly binds to NBR1 and is degraded by selective autophagy dependent on the phase separation of SQSTM1/p62. This process, named vault-phagy, is related to nonalcoholic steatohepatitis (NASH)-derived hepatocellular carcinoma.
Article
Multidisciplinary Sciences
Ryosuke Ishimura, Sota Ito, Gaoxin Mao, Satoko Komatsu-Hirota, Toshifumi Inada, Nobuo N. Noda, Masaaki Komatsu
Summary: Research has shown that UFM1 plays a role in processes such as endoplasmic reticulum-associated protein degradation, ribosome-associated protein quality control, and ER-phagy, and the UFM1 E3 complex is involved in both ufmylation and ER-RQC.
Article
Microbiology
Michitaka Suzuki, Tomoko Funakoshi, Keigo Kumagai, Masaaki Komatsu, Satoshi Waguri
Summary: Chlamydia trachomatis infection can be regulated by autophagy-related (ATG) genes. Depletion of ATG9A suppressed C. trachomatis growth in HeLa cells, and this growth was restored by re-expressing ATG9A or an ATG9A mutant. The depletion of lipid transfer proteins ATG2A/B did not significantly alter the growth, highlighting the non-autophagic function of ATG9A in supporting C. trachomatis infection. Re-expression of a mutant lacking an N-terminal adapter protein-binding domain did not rescue C. trachomatis growth, emphasizing the importance of this domain. These findings suggest that the proper trafficking of ATG9A assists C. trachomatis growth in the inclusion.
MICROBIOLOGY SPECTRUM
(2023)
Review
Biochemistry & Molecular Biology
Reo Kurusu, Hideaki Morishita, Masaaki Komatsu
Summary: Cellular zoning and the formation of membraneless organelles play crucial roles in regulating biochemical reactions inside cells, with p62 bodies maintaining cellular homeostasis through selective autophagy and activating the anti-oxidative stress response.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Ge Peng, Saya Tsukamoto, Risa Ikutama, Hai Le Thanh Nguyen, Yoshie Umehara, Juan V. Trujillo-Paez, Hainan Yue, Miho Takahashi, Takasuke Ogawa, Ryoma Kishi, Mitsutoshi Tominaga, Kenji Takamori, Jiro Kitaura, Shun Kageyama, Masaaki Komatsu, Ko Okumura, Hideoki Ogawa, Shigaku Ikeda, Francois Niyonsaba
Summary: A study found that autophagy in keratinocytes is restrained in patients with atopic dermatitis (AD) and mouse models of AD. Human β-defensin-3 (hBD-3) alleviates the impairment of the tight junction barrier through activation of keratinocyte autophagy, and reduces skin inflammation. This suggests that autophagy contributes to the pathogenesis of AD, and hBD-3 could be used therapeutically.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Shun-Suke Sakai, Atsushi Hasegawa, Ryosuke Ishimura, Naoki Tamura, Shun Kageyama, Satoko Komatsu-Hirota, Manabu Abe, Yiwei Ling, Shujiro Okuda, Manabu Funayama, Mika Kikkawa, Yoshiki Miura, Kenji Sakimura, Ichiei Narita, Satoshi Waguri, Ritsuko Shimizu, Masaaki Komatsu
Summary: A study found that the copy number duplication of ATG2B and GSKIP genes is associated with myeloproliferative neoplasm (MPN). Mice lacking both Atg2b and Gskip genes showed decreased hematopoiesis, leading to fetal death and anemia. The number of hematopoietic stem cells (HSCs), especially long-term HSCs, was significantly decreased due to increased cell death. The results demonstrate the synergistic effect of Atg2b and Gskip in maintaining the pool size of HSCs.
MOLECULAR AND CELLULAR BIOLOGY
(2022)