Article
Multidisciplinary Sciences
Joao Vasco Ferreira, Ana da Rosa Soares, Jose Ramalho, Catarina Maximo Carvalho, Maria Helena Cardoso, Petra Pintado, Ana Sofia Carvalho, Hans Christian Beck, Rune Matthiesen, Monica Zuzarte, Henrique Girao, Guillaume van Niel, Paulo Pereira
Summary: This article describes a mechanism in which proteins containing a KFERQ motif are loaded into a specific type of exosomes dependent on the membrane protein LAMP2A. This mechanism facilitates the transfer of hypoxia signaling to normoxic cells and provides a method for interorgan transfer of exosomes by tagging proteins with KFERQ-like sequences.
Article
Environmental Sciences
Zeyu Hu, Wanjing Xu, Jingjing Zhang, Yanling Tang, Hengrui Xing, Panpan Xu, Yue Ma, Qiang Niu
Summary: Excessive fluoride exposure impairs lysosomal biogenesis and autophagic degradation in the liver, leading to apoptosis. Transcription factor E3 (TFE3) plays a crucial role in regulating hepatocyte lysosomal biogenesis. Inhibition of TFE3 nuclear translocation by fluoride exposure results in compromised lysosomal function and impaired autophagic degradation, which can be restored by mTOR inhibitors rapamycin and Ad-TFE3. Therefore, TFE3 may be a potential therapeutic target for fluoride-induced hepatotoxicity.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Oncology
Manuela Zangrossi, Patrizia Romani, Probir Chakravarty, Colin D. H. Ratcliffe, Steven Hooper, Martina Dori, Mattia Forcato, Silvio Bicciato, Sirio Dupont, Erik Sahai, Marco Montagner
Summary: Many estrogen receptor-positive breast cancer patients experience relapses at the metastatic site even up to 20 years after primary tumor removal, a phenomenon known as metastatic dormancy. The molecule EphB6 has been identified as supporting the survival of disseminated dormant cancer cells, while the TFEB-lysosomal axis plays a crucial role in sustaining the survival of dormant cancer cells.
Review
Biochemistry & Molecular Biology
Yungang Lan, Wenqi He, Gaili Wang, Zhenzhen Wang, Yuzhu Chen, Feng Gao, Deguang Song
Summary: This review summarizes the experimental evidence demonstrating the correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Jonathan. M. M. Memme, Victoria. C. C. Sanfrancesco, David. A. A. Hood
Summary: Mitochondrial function is crucial for overall health and the mitochondrial unfolded protein response (UPRmt) plays a significant role in maintaining mitochondrial quality control. In this study, the transcription factor ATF4 was found to regulate mitochondrial homeostasis and myotube formation in muscle cells. ATF4 also facilitated enhanced mitochondrial networking, protein handling, and clearance of dysfunctional organelles, ultimately leading to the formation of a smaller pool of high-functioning mitochondria that are more responsive to contractile activity. These findings expand our understanding of ATF4 beyond its known functions and highlight its importance in regulating mitochondrial morphology, lysosomal biogenesis, and mitophagy in muscle cells.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
David Kader Sidibe, Vineet Vinay Kulkarni, Audrey Dong, Jessica Brandt Herr, Maria Chalokh Vogel, Max Henry Stempel, Sandra Maday
Summary: In this study, live-cell imaging in primary neurons reveals that BDNF stimulates autophagic flux in axons by activating the retrograde pathway for autophagy. However, autophagosomes do not appear to carry BDNF cargo, suggesting that they have a different role in neurotrophic processes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Stephanie Alexia Cristina Silva Santos, Pedro Muanis Persechini, Bianca Monteiro Henriques-Santos, Victoria Gabriela Bello-Santos, Newton G. Castro, Julia Costa de Sousa, Fernando Ariel Genta, Marcelo Felippe Santiago, Robson Coutinho-Silva, Luiz Eduardo Baggio Savio, Eleonora Kurtenbach
Summary: The activation of P2X7 receptor in immune cells is associated with lysosomal dysfunction and leakage. This study reveals that the P2X7 receptor and pannexin-1 channels mediate calcium influx, leading to the activation of specific ion channels on the membranes of endosomes and lysosomes, resulting in lysosomal dysfunction and cathepsin release.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, Research & Experimental
Giancarlo Parenti, Diego L. Medina, Andrea Ballabio
Summary: Lysosomal storage diseases are metabolic disorders caused by deficiencies in lysosomal function components. Understanding of lysosomal biology has evolved from organelles involved in catabolic pathways to dynamic elements involved in multiple cellular functions and capable of adapting to environmental stimuli. Novel technologies based on high-throughput approaches have greatly contributed to the characterization of lysosomal biology and dysfunction.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Sara Awan, Magalie Lambert, Ali Imtiaz, Fabien Alpy, Catherine Tomasetto, Mustapha Oulad-Abdelghani, Christine Schaeffer, Chloe Moritz, Diane Julien-David, Souad Najib, Laurent O. Martinez, Rachel L. Matz, Xavier Collet, Roberto Silva-Rojas, Johann Bohm, Joachim Herz, Jerome Terrand, Philippe Boucher
Summary: The study reveals the crucial role of Wnt5a in maintaining cholesterol homeostasis and preventing the formation of atherosclerosis by regulating lysosomal cholesterol export, metabolic signaling, and cholesterol supply.
CIRCULATION RESEARCH
(2022)
Article
Immunology
Asmaa Badr, Mostafa Eltobgy, Kathrin Krause, Kaitlin Hamilton, Shady Estfanous, Kylene P. Daily, Arwa Abu Khweek, Ahmad Hegazi, Midhun N. K. Anne, Cierra Carafice, Frank Robledo-Avila, Youssra Saqr, Xiaoli Zhang, Tracey L. Bonfield, Mikhail A. Gavrilin, Santiago Partida-Sanchez, Stephanie Seveau, Estelle Cormet-Boyaka, Amal O. Amer
Summary: Cystic fibrosis (CF) macrophages show defects in clearing bacteria and autophagy process. CFTR is recruited to autophagosomes and improves autophagy flux, lysosomal acidification, function, and bacterial clearance. These findings clarify the role of CFTR in maintaining cellular acidification and autophagy process.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Orthopedics
M. Y. Ansari, H. C. Ball, S. J. Wase, K. Novak, T. M. Haqqi
Summary: Lysosomal dysfunction in aged and OA cartilage leads to chondrocyte apoptosis, increased oxidative stress, and accumulation of dysfunctional mitochondria. Inhibiting lysosomal function results in BAX-mediated mitochondrial damage and release of Cytochrome c, inducing apoptosis in chondrocytes. Restoring lysosomal function and inhibiting BAX may be a potential therapeutic approach for OA.
OSTEOARTHRITIS AND CARTILAGE
(2021)
Article
Biochemistry & Molecular Biology
Anika Reifschneider, Sophie Robinson, Bettina van Lengerich, Johannes Gnoerich, Todd Logan, Steffanie Heindl, Miriam A. Vogt, Endy Weidinger, Lina Riedl, Karin Wind, Artem Zatcepin, Ida Pesaemaa, Sophie Haberl, Brigitte Nuscher, Gernot Kleinberger, Julien Klimmt, Julia K. Goetzl, Arthur Liesz, Katharina Buerger, Matthias Brendel, Johannes Levin, Janine Diehl-Schmid, Jung Suh, Gilbert Di Paolo, Joseph W. Lewcock, Kathryn M. Monroe, Dominik Paquet, Anja Capell, Christian Haass
Summary: Microglial hyperactivation caused by haploinsufficiency of the progranulin encoding gene does not promote neurotoxicity, but rather plays a neuroprotective role. Intervening with the TREM2-dependent microglial state can reduce microglia hyperactivation.
Review
Biochemistry & Molecular Biology
Olga Amaral, Mariana Martins, Ana Rita Oliveira, Ana Joana Duarte, Ines Mondragao-Rodrigues, M. Fatima Macedo
Summary: Since its discovery in 1955, the understanding of the lysosome has significantly deepened. It is now recognized as a crucial component for cellular signaling and energy metabolism, challenging the previous perception of it being solely a waste removal system. A summarized review of lysosome biology is necessary to comprehend its role in lysosomal disease.
Article
Biochemistry & Molecular Biology
Yanhua Kang, Tingyue Wu, Yan He, Yunfan He, Dongjiu Zhao
Summary: Elf4 is an important transcription factor induced by Staphylococcus aureus in macrophages, which enhances lysosomal function and increases the capacity of macrophages to eliminate intracellular pathogens.
Article
Plant Sciences
Jianhui Wang, Rui Xu, Shuangping Qiu, Weichun Wang, Fan Zheng
Summary: In this study, a homologous gene of AtTT8 was identified in blood orange (Citrus sinensis cv 'Tarocco') fruit. The mRNA levels of TT8 were significantly higher in 'Tarocco' fruit than in mutant fruit lacking pigment. An alternative splicing transcript, Delta 15-TT8, was also found and its mRNA levels were higher in mutant fruit. The study demonstrated the role of TT8 in regulating anthocyanin biosynthesis and its transport, while the dysfunctional Delta 15-TT8 may act as a negative feedback to downregulate TT8 expression and limit anthocyanin accumulation.
HORTICULTURE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Takahiro Sasaki, Masamitsu Shimazawa, Hiromitsu Kanamori, Yoshihisa Yamada, Anri Nishinaka, Yoshiki Kuse, Genjiro Suzuki, Tomomi Masuda, Shinsuke Nakamura, Masato Hosokawa, Shinya Minatoguchi, Hideaki Hara
SCIENTIFIC REPORTS
(2020)
Article
Biology
Genjiro Suzuki, Sei Imura, Masato Hosokawa, Ryu Katsumata, Takashi Nonaka, Shin-Ichi Hisanaga, Yasushi Saeki, Masato Hasegawa
Article
Neurosciences
Tomoko Tanaka, Shinobu Hirai, Masato Hosokawa, Takashi Saito, Hiroshi Sakuma, Takaomi Saido, Masato Hasegawa, Haruo Okado
Summary: The study found that maternal separation can induce early AD-related pathology by affecting microglial activation and the vascular system.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Clinical Neurology
Masato Hosokawa, Masami Masuda-Suzukake, Hiroshi Shitara, Aki Shimozawa, Genjiro Suzuki, Hiromi Kondo, Takashi Nonaka, William Campbell, Tetsuaki Arai, Masato Hasegawa
Summary: The phenomenon of 'prion-like propagation' is attracting attention as a new mechanism in neurodegenerative diseases. Researchers have generated mice that express both 3R and 4R tau and successfully reproduced the pathology of Alzheimer's disease, corticobasal degeneration, and Pick's disease by injecting brain samples from patients with different tauopathies. These models are valuable for understanding the propagation mechanism of tau pathology and discovering new therapeutic agents.
Article
Biochemical Research Methods
Kazuki Uchida, Kazunori Morikawa, Yoshio Muguruma, Masato Hosokawa, Kaname Tsutsumiuchi, Daita Kaneda, Yoshio Hashizume, Hiroyasu Akatsu, Koichi Inoue
Summary: This study developed a quantitative procedure for analyzing peripheral acetylated alpha-Syn using liquid chromatography coupled with tandem mass spectrometry, and measured the levels of Ac-alpha-Syn in serum samples from postmortem AD patients. The results showed an insignificant difference in Ac-alpha-Syn levels between the AD group and the control group.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Shiori Awa, Genjiro Suzuki, Masami Masuda-Suzukake, Takashi Nonaka, Minoru Saito, Masato Hasegawa
Summary: This study investigated the early phase of phosphorylated alpha-synuclein accumulation by injecting alpha-synuclein fibrils into the brains of wild-type mice. The results showed that phosphorylated alpha-synuclein appeared within a few days after injection, initially in presynaptic regions and subsequently extending its localization to axons and cell bodies.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Kazunori Sano, Yasushi Iwasaki, Yuta Yamashita, Keiichi Irie, Masato Hosokawa, Katsuya Satoh, Kenichi Mishima
Summary: The phosphorylation of alpha synuclein at Y136 in the Lewy body dementia brain is mediated by the unexpected kinase activity of CK2. CK2 can promote aggregate formation of r-alpha Syn with phosphorylation at S129 and Y136, while its inhibition attenuates the formation of aggregates with S129 phosphorylation and unexpectedly increases phosphorylation at Y136.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yoshinori Tanaka, Shun-ya Kusumoto, Yuki Honma, Kosuke Takeya, Masumi Eto
Summary: In this study, we found that PGRN overexpression suppresses autophagic flux and worsens the pathology of neurodegenerative diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Mai Hazekawa, Takuya Nishinakagawa, Masato Hosokawa, Daisuke Ishibashi
Summary: This study aimed to deliver therapeutic siRNAs for melanoma lung metastases using autologous serum-derived exosomes. The results showed that siRNA-loaded exosomes prepared with autologous serum-derived exosomes significantly decreased the number of metastatic lung colonies. Autologous serum-derived exosomes, which have high organ accumulation, could potentially be used as efficient carriers of therapeutic siRNAs for melanoma patients with lung metastases.
Article
Biochemistry & Molecular Biology
Yoshinori Tanaka, Hirotsugu Hino, Kosuke Takeya, Masumi Eto
Summary: Macroautophagy, a cellular degradation system, plays a crucial role in disease development. This study investigates the formation of autolysosomes and their regulation by autophagosome-lysosome fusion. The researchers suggest that vacuole-like autolysosomes induced by specific drugs could be used as a tool to evaluate autophagosome-lysosome fusion and study the effects of PGRN in autophagy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Yoshinori Tanaka, Shun-ichi Ito, Yuki Honma, Masato Hasegawa, Fuyuki Kametani, Genjiro Suzuki, Lina Kozuma, Kosuke Takeya, Masumi Eto
Summary: The secretion of TDP-43 is stimulated by the inhibition of the autophagy-lysosomal pathway driven by the protein progranulin (PGRN). This dysregulation promotes the cell-to-cell spread of TDP-43 and may contribute to the progression of amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Clinical Neurology
Masami Masuda-Suzukake, Genjiro Suzuki, Masato Hosokawa, Takashi Nonaka, Michel Goedert, Masato Hasegawa
BRAIN COMMUNICATIONS
(2020)