Article
Cell Biology
Bhaskar Saha, Michelle Salemi, Geneva L. Williams, Seeun Oh, Michael L. Paffett, Brett Phinney, Michael A. Mandell
Summary: The study used proteomics to identify TRIM5a-interacting partners and found that TRIM5 is involved in mitophagy and maintaining cellular homeostasis, in addition to its known role in antiviral defense.
Article
Cell Biology
Alba Sabate-Perez, Montserrat Romero, Paula Sanchez-Fernandez-de-Landa, Stefania Carobbio, Michail Mouratidis, David Sala, Pablo Engel, Josep A. Villena, Sam Virtue, Antonio Vidal-Puig, Manuel Palacin, Xavier Testar, Antonio Zorzano
Summary: The study reveals a novel molecular mechanism by which TP53INP2 regulates PPARG activity and brown adipogenesis through autophagy, and demonstrates the importance of TP53INP2 in maintaining thermogenic capacity and preventing lipid accumulation in brown adipose tissue. These findings provide insights into the therapeutic strategies against obesity and its metabolic complications.
Article
Biochemistry & Molecular Biology
Tetsushi Kataura, Elsje G. Otten, Yoana Rabanal-Ruiz, Elias Adriaenssens, Francesca Urselli, Filippo Scialo, Lanyu Fan, Graham R. Smith, William M. Dawson, Xingxiang Chen, Wyatt W. Yue, Agnieszka K. Bronowska, Bernadette Carroll, Sascha Martens, Michael Lazarou, Viktor Korolchuk
Summary: Mitophagy is essential for maintaining cellular homeostasis. The best characterised pathway involves the stabilisation of PINK1 and recruitment of Parkin to damaged mitochondria. NDP52 recognises ubiquitinated mitochondrial proteins and initiates autophagic vesicle formation. This study found that oxidation of NDP52 is crucial for efficient PINK1/Parkin-dependent mitophagy, and proposed that redox sensing allows mitophagy to function as an oxidative stress response.
Article
Biochemistry & Molecular Biology
Eric N. Bunker, Francois Le Guerroue, Chunxin Wang, Marie-Paule Strub, Achim Werner, Nico Tjandra, Richard J. Youle
Summary: This study reveals the mechanisms of Nix-mediated mitophagy and the importance of both the LIR and MER regions. The MER region interacts with the autophagy effector WIPI2 and recruits it to mitochondria, while the LIR region converts the distribution of WIPI2 on mitochondria into puncta. These findings provide valuable insights into the process of Nix-induced mitophagy.
Article
Biochemistry & Molecular Biology
Ashari R. Kannangara, Daniel M. Poole, Colten M. McEwan, Joshua C. Youngs, Vajira K. Weerasekara, Alex M. Thornock, Misael T. Lazaro, Eranga R. Balasooriya, Laura M. Oh, Erik J. Soderblom, Jonathan J. Lee, Daniel L. Simmons, Joshua L. Andersen
Summary: ATG9A, a multi-pass transmembrane protein, plays a crucial role in regulating autophagy. It interacts with members of the ULK1 complex and regulators of membrane fusion and vesicle trafficking, marking pathways of ATG9A trafficking through different cellular systems. ATG9A interacts with ATG13-ATG101 independently of ULK1, and deletion of ATG13 or ATG101 causes abnormal accumulation of ATG9A at stalled clusters of certain proteins, which can be rescued by a mutant form of ATG13 lacking ULK1 binding capability.
Article
Biochemistry & Molecular Biology
Cheong-Yong Yun, Nahyun Choi, Jae Un Lee, Eun Jung Lee, Ji Young Kim, Won Jun Choi, Sang Ho Oh, Jong-Hyuk Sung
Summary: This study demonstrated that the marliolide derivative DMF02 can induce melanosome degradation through autophagy pathway by activating Nrf2, leading to reduced melanin pigmentation. Additionally, DMF02 was effective in reducing UVB-induced hyperpigmentation and regulating melanosome degradation via suppression of p62. These findings suggest that Nrf2 activators could be promising therapeutic agents for reducing hyperpigmentation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Jiamei Zhang, Lu Han, Qinmei Ma, Xiaoping Wang, Jialin Yu, Yanan Xu, Xu Zhang, Xiaoling Wu, Guangcun Deng
Summary: It has been found that RIP3 plays a crucial role in fighting against Mycobacterium tuberculosis (M.tb) infection by promoting autophagy, which enhances host clearance of the bacteria.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
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.
Retraction
Biochemistry & Molecular Biology
A. Caccamo, E. Ferreira, C. Branca, S. Oddo
Summary: The article has been retracted by the Editor-in-Chief and publisher.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Qing Shi, Xiaofeng Jin, Pingzhao Zhang, Qian Li, Zeheng Lv, Yan Ding, Huiying He, Yijun Wang, Yuanlong He, Xiaying Zhao, Shi-Min Zhao, Yao Li, Kun Gao, Chenji Wang
Summary: This study reveals that SPOP mutations induce non-degradative ubiquitination of p62, leading to suppression of p62-dependent autophagy and decreased Nrf2-mediated transcriptional activation of antioxidant genes, thus promoting tumor formation in SPOP-mutated PCa.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Neurosciences
Haifeng Lu, Yugang Wang, Hua Fan, Yiqing Wang, Shenghao Fan, Shimin Hu, Haitao Shen, Haiying Li, Qun Xue, Jianqiang Ni, Qi Fang, Gang Chen
Summary: The mechanisms underlying the regulation of circadian rhythms in relation to the development of brain disorders such as depression, autism, and stroke remain unclear. Glutamate systems and autophagy are thought to play important roles in the pathogenesis of stroke. This study found that GluA1 expression was decreased and autophagic activity was increased during the active phase of stroke in male mouse models. Inhibition of autophagy increased the infarct volume, while activation of autophagy decreased it. Additionally, the circadian rhythm gene Per1 was found to influence GluA1 expression and autophagic activity in stroke.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell Biology
Liyan Gong, Kaihua Wang, Mengcheng Wang, Ronggui Hu, Huaguang Li, Daming Gao, Moubin Lin
Summary: The study identified the CUL5-ASB6 complex as a mediator of p62 ubiquitination and degradation, with overexpression of ASB6 inhibiting cell proliferation by reducing p62 protein level and affecting autophagy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Nora Mohamed Elkenawy, Heba Ramadan Ghaiad, Sherehan Mohamed Ibrahim, Ramy Karam Aziz, Eman Rashad, Walaa Ahmed Eraqi
Summary: This study aimed to investigate the radioprotective effects and related mechanisms of ubiquinol against radiation-induced splenic tissue injury. The results showed that ubiquinol can protect the spleen from radiation damage by enhancing antioxidant pathways, promoting autophagy, and enhancing survival pathways.
INTERNATIONAL IMMUNOPHARMACOLOGY
(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
Cell Biology
Shaogui Wang, Xiaojuan Chao, Xiaoxiao Jiang, Tiantian Wang, Yssa Rodriguez, Ling Yang, Pal Pacher, Hong-Min Ni, Wen-Xing Ding
Summary: VMP1 plays a crucial role in the pathogenesis of pancreatitis by regulating autophagic degradation and ER stress, and its deficiency promotes inflammation and fibrosis. The study revealed the importance of VMP1 in modulating pancreatitis through the NFE2L2/Nrf2 pathway.
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)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)
