Article
Biochemistry & Molecular Biology
Seon Ae Jeong, Jisoo Song, Jiyeon Ham, Garam An, Gwonhwa Song, Whasun Lim
Summary: This study found that tetraconazole, as a fungicide, not only directly affects plants and fruits, but also indirectly affects milk production in cows. Tetraconazole induces apoptosis, inhibits cell survival and proliferation, and disrupts calcium homeostasis and mitochondrial function in bovine mammary epithelial cells (MAC-T). It also alters the expression of proliferation-related proteins and signaling pathways, as well as impairs autophagy functioning in MAC-T cells. These findings suggest that tetraconazole exposure can lead to a failure of milk production in bovine mammary epithelial cells.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Environmental Sciences
Daqian Yang, Qingyue Yang, Ning Fu, Siyu Li, Bing Han, Yan Liu, Yuqing Tang, Xinyu Guo, Zhanjun Lv, Zhigang Zhang
Summary: Chronic exposure to hexavalent chromium was found to cause heart dysfunction in rats, characterized by hematological variations, oxidative stress, cardiomyocyte apoptosis, and mitochondrial impairment. Additionally, the expression of certain proteins like Sesn2, PGC-1α, and Nrf2 was suppressed in chromium-treated rat hearts, potentially contributing to the observed dysfunction.
Article
Biology
Masak Takaine, Hiromi Imamura, Satoshi Yoshida
Summary: This study demonstrates the importance of cellular ATP homeostasis in maintaining protein stability, and identifies AMPK and ADK as key factors in preventing proteinopathies.
Review
Medicine, Research & Experimental
Rachit Jain, Nusrat Begum, Kamatham Pushpa Tryphena, Shashi Bala Singh, Saurabh Srivastava, Sachchida Nand Rai, Emanuel Vamanu, Dharmendra Kumar Khatri
Summary: Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons and the accumulation of alpha-synuclein protein in Lewy bodies, leading to mitochondrial dysfunction. Mitochondrial dynamics, including movement within and between cells, are impaired in PD. Various proteins, enzymes, and molecules are involved in regulating mitochondrial movement. Understanding these pathways is crucial for developing mitochondrial transplant therapy for PD. Techniques such as mitochondrial coculture and mitoception are being explored for their potential translational value. This review focuses on the importance of understanding intercellular and intracellular mitochondrial dynamics in PD and highlights the potential of mitochondrial transplant therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Somya Patro, Sujay Ratna, Hianny A. Yamamoto, Andrew T. Ebenezer, Dillon S. Ferguson, Amanpreet Kaur, Brendan C. McIntyre, Ryan Snow, Maria E. Solesio
Summary: Alzheimer's Disease is the most common neurodegenerative disorder in society, with increasing incidence expected as the population ages. Mitochondrial dysfunction has been widely described in the brains of AD patients, and may act as a trigger for early events in the disease. Modulating ATP synthase pharmacologically could be a potential strategy to prevent mitochondrial dysfunction in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Jielin Deng, Yunqiu Jiang, Zhen Bouman Chen, June-Wha Rhee, Yingfeng Deng, Zhao V. Wang
Summary: Electrophysiological and structural disruptions in cardiac arrhythmias are closely related to mitochondrial dysfunction. Mitochondria are responsible for producing ATP, which is essential for the continuous electrical activity in the heart. Impaired supply-demand relationship and progressive mitochondrial dysfunction in arrhythmias result in reduced ATP production and increased reactive oxidative species generation. Pathological changes in gap junctions and inflammatory signaling disrupt ion homeostasis, membrane excitability, and cardiac structure, leading to impaired cardiac electrical homeostasis. This review focuses on the electrical and molecular mechanisms of cardiac arrhythmias, highlighting the role of mitochondrial dysfunction in ionic regulation and gap junction action. The article explores inherited and acquired mitochondrial dysfunction and its impact on different types of arrhythmias, as well as the involvement of mitochondria in bradyarrhythmia and tachyarrhythmia caused by factors like aging, gut microbiome, cardiac reperfusion injury, and electrical stimulation.
Article
Endocrinology & Metabolism
A-Hyeon Lee, Ju Hee Oh, Hyun Sung Kim, Jeong-Hun Shin, Eileen L. Yoon, Dae Won Jun
Summary: This study found that patients with NAFLD have mitochondrial dysfunction, and the mtDNA copy number of peripheral blood mononuclear cells and mitochondrial ATP inhibition substrate test can be used as biomarkers for assessing mitochondrial dysfunction in these patients. Hepatic mRNA transcriptome analysis showed increased expression of genes related to mitochondrial functions in NAFLD patients compared to non-alcoholic fatty liver disease patients. Gene set enrichment analysis revealed that these upregulated genes are related to the pathways of the TCA cycle and DNA replication.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biology
Michael W. Country, Michael G. Jonz
Summary: By studying the responses of goldfish and rainbow trout retinal cells to hypoxia, it was found that goldfish maintain [Ca2+](i) stably by using mitochondrial ATP-dependent K+ channels (mK(ATP)) to resist excitotoxicity, while rainbow trout experience a rapid increase in [Ca2+](i) during hypoxia, which can be life-threatening.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2021)
Article
Food Science & Technology
Hanne Vissenaekens, Guy Smagghe, Hanne Criel, Charlotte Grootaert, Katleen Raes, Andreja Rajkovic, Geert Goeminne, Nico Boon, Kristof De Schutter, John Van Camp
Summary: The study demonstrates that quercetin can partially restore mitochondrial dysfunction, especially FCCP-induced dysfunction, in intestinal cells by accumulating in the mitochondria.
FOOD RESEARCH INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Erica L. Underwood, John B. Redell, Kimberly N. Hood, Mark E. Maynard, Michael Hylin, M. Neal Waxham, Jing Zhao, Anthony N. Moore, Pramod K. Dash
Summary: Prominent features of long-term memory formation include protein synthesis, gene expression, enhanced neurotransmitter release, increased excitability, and formation of new synapses. This study found that mitochondrial respiration and dynamics play a crucial role in memory formation. Fear training was shown to increase mitochondrial oxygen consumption (OCR) in specific regions of the hippocampus, and inhibition of dynamin-related protein 1 (Drp1) decreased OCR and impaired contextual fear memory. These findings suggest that enhanced energy production in pre-synaptic terminals is necessary for context fear memory.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Zhou Zhou, Kailiang Zhang, Zhiheng Liu, Xu Gao, Kai Huang, Chen Chen, Daowen Wang, Qinglin Yang, Qinqiang Long
Summary: ATPAF1 is essential for maintaining cardiac structure and function in animals. Its deficiency leads to decreased ATP synthase content and impaired mitochondrial respiratory capacity, resulting in structural abnormalities in mitochondria and impaired cardiac function in mice.
Article
Peripheral Vascular Disease
Vivien Becker, Xin Hui, Lisa Nalbach, Emmanuel Ampofo, Peter Lipp, Michael D. Menger, Matthias W. Laschke, Yuan Gu
Summary: The study demonstrated that linalool can effectively inhibit the angiogenic activity of endothelial cells, which may be mediated by regulating the ERK signaling pathway, downregulating intracellular ATP levels, and activating TRPM8 channels.
Article
Chemistry, Applied
Ke Zhang, Xingtao Zhou, Junqiao Wang, Yujia Zhou, Wucheng Qi, Haihong Chen, Shaoping Nie, Mingyong Xie
Summary: The Dendrobium officinale polysaccharide (DOP) inhibits proliferation of colon cancer cells by disrupting mitochondrial function and increasing autophagy levels through activation of AMPK/mTOR pathway. Additionally, pretreatment with antioxidant N-acetyl-L-cysteine reverses the cytotoxic effect and mitochondrial dysfunction induced by DOP in CT26 cells.
CARBOHYDRATE POLYMERS
(2021)
Article
Multidisciplinary Sciences
Dayne A. Beccano-Kelly, Marta Cherubini, Yassine Mousba, Kaitlyn M. L. Cramb, Stefania Giussani, Maria Claudia Caiazza, Pavandeep Rai, Siv Vingill, Nora Bengoa-Vergniory, Bryan Ng, Gabriele Corda, Abhirup Banerjee, Jane Vowles, Sally Cowley, Richard Wade-Martins
Summary: This article describes early physiological perturbations in patient-derived induced pluripotent stem cell (iPSC)-dopamine neurons, highlighting the calcium dysregulation and mitochondrial failure that may underlie the vulnerability of dopamine neurons in Parkinson's disease (PD).
Review
Biochemistry & Molecular Biology
Tsung-Hsien Chen, Kok-Yean Koh, Kurt Ming-Chao Lin, Chu-Kuang Chou
Summary: This article discusses the association between impaired mitochondrial function and skeletal muscle disorders, and emphasizes the need for further research to determine the specific clinical benefits of mitochondrial therapy in the treatment of skeletal muscle disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Hiromi Imamura, Shuichiro Sakamoto, Tomoki Yoshida, Yusuke Matsui, Silvia Penuela, Dale W. Laird, Shin Mizukami, Kazuya Kikuchi, Akira Kakizuka
Article
Biochemistry & Molecular Biology
Yafei Liu, Wai Tuck Soh, Jun-ichi Kishikawa, Mika Hirose, Emi E. Nakayama, Songling Li, Miwa Sasai, Tatsuya Suzuki, Asa Tada, Akemi Arakawa, Sumiko Matsuoka, Kanako Akamatsu, Makoto Matsuda, Chikako Ono, Shiho Torii, Kazuki Kishida, Hui Jin, Wataru Nakai, Noriko Arase, Atsushi Nakagawa, Maki Matsumoto, Yukoh Nakazaki, Yasuhiro Shindo, Masako Kohyama, Keisuke Tomii, Koichiro Ohmura, Shiro Ohshima, Toru Okamoto, Masahiro Yamamoto, Hironori Nakagami, Yoshiharu Matsuura, Atsushi Nakagawa, Takayuki Kato, Masato Okada, Daron M. Standley, Tatsuo Shioda, Hisashi Arase
Summary: The research found that antibodies against different domains of the SARS-CoV-2 spike protein have different effects, with some antibodies inducing an open conformation of the RBD and enhancing the virus infectivity. Structural and mutational analysis revealed the mechanisms of these antibodies, and infectivity-enhancing antibodies were detected at higher levels in severe patients.
Article
Multidisciplinary Sciences
J. Kishikawa, A. Nakanishi, A. Nakano, S. Saeki, A. Furuta, T. Kato, K. Mistuoka, K. Yokoyama
Summary: The authors report the atomic models of 18 catalytic intermediates of the V-1 domain of V/A-ATPase under different reaction conditions, determined by single particle cryo-EM. The models reveal that the rotor does not immediately rotate after the binding of ATP, but undergoes multiple events including ATP hydrolysis and release of ADP and Pi during the rotation process.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Masak Takaine, Hiromi Imamura, Satoshi Yoshida
Summary: This study demonstrates the importance of cellular ATP homeostasis in maintaining protein stability, and identifies AMPK and ADK as key factors in preventing proteinopathies.
Article
Multidisciplinary Sciences
Jun-ichi Kishikawa, Moe Ishikawa, Takahiro Masuya, Masatoshi Murai, Yuki Kitazumi, Nicole L. Butler, Takayuki Kato, Blanca Barquera, Hideto Miyoshi
Summary: The Na+-pumping NADH-ubiquinone oxidoreductase (Na+-NQR) is a unique respiratory enzyme found in many pathogenic bacteria. In this study, high-resolution cryo-EM structures of Na+-NQR from V. cholerae with or without a bound inhibitor are presented, revealing the arrangement of all redox cofactors and the presence of a 2Fe-2S cluster. The study also demonstrates the high flexibility of NqrF and the binding of specific inhibitors to the N-terminal region of NqrB.
NATURE COMMUNICATIONS
(2022)
Review
Microscopy
Christoph Gerle, Jun-ichi Kishikawa, Tomoko Yamaguchi, Atsuko Nakanishi, Orkun coruh, Fumiaki Makino, Tomoko Miyata, Akihiro Kawamoto, Ken Yokoyama, Keiichi Namba, Genji Kurisu, Takayuki Kato
Summary: Progress in structural membrane biology has been greatly enhanced by the "Resolution Revolution" in cryo-electron microscopy (cryo-EM), particularly the use of single-particle analysis for determining atomic models of multisubunit membrane protein complexes. However, there is a growing need for new and affordable cryo-electron microscopes to meet the increasing demand for cryo-EM machine time.
Article
Biochemistry & Molecular Biology
Tatsuro Nishikino, Norihiro Takekawa, Duy Phuoc Tran, Jun-ichi Kishikawa, Mika Hirose, Sakura Onoe, Seiji Kojima, Michio Homma, Akio Kitao, Takayuki Kato, Katsumi Imada
Summary: Motile bacteria swim towards favorable environments using a rotating flagellum driven by a motor. The motor consists of a rotor and a stator, with the torque generated by the interaction between the rotor and the stator induced by ion flow. Recent cryo-EM studies on the stators from mesophiles revealed their composition, while low-resolution EM analysis showed that hyperthermophilic MotA forms a tetramer. The cryo-EM structure of MotA from the hyperthermophilic bacterium Aquifex aeolicus (Aa-MotA) was determined, showing it forms a pentamer and can assemble into a stator complex without MotB. The hydrophobic nature of MotA is crucial for stabilizing hyperthermophilic Aa-MotA.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Atsuko Nakanishi, Jun-ichi Kishikawa, Kaoru Mitsuoka, Ken Yokoyama
Summary: This study used cryo-electron microscopy to reveal the intermediate structures of V/A-ATPase during the transition from the ground state to the steady state, providing insights into the sequential binding of ATP to its catalytic sites. These findings enhance our understanding of the initial activation processes of enzymes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Developmental Biology
Maimaiti Mikeli, Makoto Fujikawa, Tsutomu Tanabe
Summary: Knocking down GPD2 lowers the cancer stemness in hepatocarcinoma and neuroblastoma cells, indicating its involvement in maintaining cancer stem cells. GPD2 may also play a role in neural stem cell maintenance. Further studies are needed to confirm these findings. GPD2 could be a potential target for cancer therapy, stem cell research, and development.
CELLS & DEVELOPMENT
(2023)
Article
Cell Biology
Emiko Urano, Yumi Itoh, Tatsuya Suzuki, Takanori Sasaki, Jun-ichi Kishikawa, Kanako Akamatsu, Yusuke Higuchi, Yusuke Sakai, Tomotaka Okamura, Shuya Mitoma, Fuminori Sugihara, Akira Takada, Mari Kimura, Shuto Nakao, Mika Hirose, Tadahiro Sasaki, Ritsuko Koketsu, Shunya Tsuji, Shota Yanagida, Tatsuo Shioda, Eiji Hara, Satoaki Matoba, Yoshiharu Matsuura, Yasunari Kanda, Hisashi Arase, Masato Okada, Junichi Takagi, Takayuki Kato, Atsushi Hoshino, Yasuhiro Yasutomi, Akatsuki Saito, Toru Okamoto
Summary: The engineered ACE2 decoy retains neutralization activity against Omicron subvariants and shows therapeutic potential for SARS-CoV-2 infection. Inhalation of aerosolized decoys improves outcomes in rodents infected with SARS-CoV-2. The engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Atsuki Nakano, Jun-ichi Kishikawa, Kaoru Mitsuoka, Ken Yokoyama
Summary: The ATP synthase FoF1 undergoes rotation in discrete 120° steps. Using cryo-EM analysis, the authors characterized intermediate structures within these 120° steps at 81°, 83°, 91°, and 101°. This shows that FoF1 undergoes a total of 15 steps in a 360° rotation, exhibiting multiple discreet movements per full rotation as opposed to one fluid motion.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Atsuki Nakano, Jun-ichi Kishikawa, Atsuko Nakanishi, Kaoru Mitsuoka, Ken Yokoyama
Summary: Adenosine triphosphate (ATP) synthases are crucial for all aerobic organisms. This study determined the cryo-electron microscopy structures of bacterial F0F1 under different reaction conditions and revealed that the unisite catalysis of bacterial F0F1 significantly differs from the kinetics of steady-state turnover.