Article
Cell Biology
Changhao Wu, Chenglong Zheng, Shiyu Chen, Zhiwei He, Hao Hua, Chengyi Sun, Chao Yu
Summary: Pancreatic cancer (PC) is a gastrointestinal tract malignant tumor with a poor prognosis. FOXQ1 has been found to be overexpressed in PC tissues and associated with poor prognosis. FOXQ1 overexpression promotes PC cell proliferation, tumor stemness, invasion, and metastasis, while FOXQ1 silencing shows the reverse effect. Mechanistic studies reveal that FOXQ1 promotes LDHA transcription to enhance aerobic glycolysis, contributing to the progression of PC.
CELL DEATH & DISEASE
(2023)
Review
Cell Biology
Xin Du, Hai Hu
Summary: 2-HG plays a significant role in 2-hydroxyglutaric aciduria, tumors with IDH1/2mt mutations, and ccRCC, being regarded as an oncometabolite. It can also accumulate in hypoxic or acidic pH conditions, and has been shown to have a vital role in the fate decision of immune cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Dolly Sharma, Mamta Singh, Reshma Rani
Summary: Lactate dehydrogenase plays a crucial role in tumor metabolism, and its inhibition may be a potential approach for anticancer therapy.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Cell Biology
Jun Li, Qian Zhang, Yupeng Guan, Dingzhun Liao, Donggen Jiang, Haiyun Xiong, Hengji Zhan, Jun Pang
Summary: The study reveals a novel molecular mechanism by which circVAMP3 promotes glycolysis and proliferation in RCC by regulating the enzymatic activity of LDHA, suggesting circVAMP3 as a biomarker and treatment target for RCC.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Qidi Chen, Min Xin, Lingjun Wang, Lin Li, Yingzhi Shen, Yan Geng, Haojie Jiang, Yang Wang, Lin Zhang, Yanyan Xu, Yu Hou, Junling Liu, Xuemei Fan
Summary: This study reveals the significant role of lactate dehydrogenase A (LDHA) in megakaryocyte (MK) maturation and platelet production, independent of lactate content. The study also provides insights into the regulation of translation by the interaction between LDHA and eukaryotic elongation factor 2 (eEF2).
Article
Biochemistry & Molecular Biology
Luis Q. Alves, Raquel Ruivo, Raul Valente, Miguel M. Fonseca, Andre M. Machado, Stephanie Plon, Nuno Monteiro, David Garcia-Parraga, Sara Ruiz-Diaz, Maria J. Sanchez-Calabuig, Alfonso Gutierrez-Adan, L. Filipe C. Castro
Summary: Mammalian sperm cells exhibit metabolic compartmentalization, with ATP production separated in different subcellular compartments. The pathways of glycolysis and oxidative phosphorylation play varying roles in sperm function across species, and the impact of ecosystem resource availability and dietary adaptations on reproductive physiology traits remains to be further explored.
Article
Biochemistry & Molecular Biology
Liang Shi, Rui Duan, Zhenhua Sun, Qiong Jia, Wenyu Wu, Feng Wang, Jianjun Liu, Hao Zhang, Xue Xue
Summary: Dysregulation of long noncoding RNAs (lncRNAs) is associated with the development and progression of human cancers. The lncRNA GLTC was identified as an interacting partner of LDHA and is required for increased glycolysis and cell viability in papillary thyroid cancer (PTC). GLTC is upregulated in PTC tissues and high expression is correlated with distant metastasis, larger tumor size, and poor prognosis. GLTC promotes LDHA enzymatic activity by inhibiting the interaction between SIRT5 and LDHA, leading to succinylation of LDHA at lysine 155 (K155). Inhibition of GLTC reverses the effects of succinylated LDHA on radioiodine (RAI) resistance. Therefore, GLTC may serve as a potential therapeutic target for enhancing RAI sensitivity in PTC treatment.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Pharmacology & Pharmacy
Maitham A. Khajah, Sarah Khushaish, Yunus A. Luqmani
Summary: This study revealed that the expression, activity, and lactate production of LDH-A and B were significantly enhanced in endocrine-resistant breast cancer cells. Targeting LDH might be an effective strategy to inhibit cancer cell motility.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Genetics & Heredity
Oh Kwang Kwon, In Hyuk Bang, So Young Choi, Ju Mi Jeon, Ann-Yae Na, Yan Gao, Sam Seok Cho, Sung Hwan Ki, Youngshik Choe, Jun Nyung Lee, Yun-Sok Ha, Eun Ju Bae, Tae Gyun Kwon, Byung-Hyun Park, Sangkyu Lee
Summary: This study reveals the reduction of SIRT5 protein expression and LDHA-K118su as a novel mechanism involved in PCa progression, which could serve as a new target to prevent CPRC progression for PCa treatment.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2023)
Article
Biotechnology & Applied Microbiology
Naoya Kataoka, Kazunobu Matsushita, Toshiharu Yakushi
Summary: In this study, a system for efficient production of 2-HG was developed using Corynebacterium glutamicum. The hgdH gene from Acidaminococcus fermentans was introduced into C. glutamicum, resulting in the biosynthesis of 2-OG. The engineered strain produced the highest reported titer and yield of 2-HG thus far under biotin- and nitrogen-limited conditions.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jianmin Wu, Xingshi Gu, Juan Zhang, Ze Mi, Zhenhu He, Yuqian Dong, Wu Ge, Kedar Ghimire, Pengfei Rong, Wei Wang, Xiaoqian Ma
Summary: 4-Octyl itaconate (4-OI) can reduce cell death and inflammation, inhibit ROS production and LDHA activity in pancreatic beta cells under oxidative stress. This finding contributes to the prevention of diabetes.
Article
Cell Biology
Clara I. Marin-Briggiler, Guillermina M. Luque, Maria G. Gervasi, Natalia Oscoz-Susino, Jessica M. Sierra, Carolina Mondillo, Ana M. Salicioni, Dario Krapf, Pablo E. Visconti, Mariano G. Buffone
Summary: Experimental results show that human sperm exhibit reduced motility and other kinematic parameters under starvation conditions, while treatment with energy recovery restores hyperactivated motility, rapidly increasing ATP and cAMP levels. This suggests that modulating sperm energy levels through such treatment may positively impact human sperm fertilizing ability in vitro.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Juan Liu, Cen Zhang, Tianliang Zhang, Chun-Yuan Chang, Jianming Wang, Ludvinna Bazile, Lanjing Zhang, Bruce G. G. Haffty, Wenwei Hu, Zhaohui Feng
Summary: The glycolytic enzyme lactate dehydrogenase A (LDHA) activates small GTPase Rac1 to promote cancer independently of its glycolytic enzyme activity. LDHA interacts with the active form of Rac1, Rac1-GTP, to inhibit Rac1-GTP interaction with its negative regulator, GTPase-activating proteins, leading to Rac1 activation. LDHA overexpression in clinical breast cancer specimens is associated with higher Rac1 activity. Inhibition of Rac1 suppresses the oncogenic effect of LDHA. Combination inhibition of LDHA enzyme activity and Rac1 activity displays a synergistic inhibitory effect on breast cancers with LDHA overexpression.
Article
Oncology
Xiao-Hong Wang, Zhong-Hua Jiang, Hong-Mei Yang, Yu Zhang, Li-Hua Xu
Summary: FOXO4 downregulation in gastric cancer is associated with poor prognosis. Restoring FOXO4 expression decreases glycolysis rate in GC cells, while silencing it increases glycolysis rate. FOXO4 is a transcriptional target of HIF-1 alpha and plays a key role in regulating glycolysis in GC.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Microbiology
Koichi Toyoda, Masayuki Inui
Summary: When transitioning from exponential to stationary growth phases, bacterial metabolism shifts from aerobic respiration to fermentation in response to limited oxygen availability. The ldhA gene in Corynebacterium glutamicum encodes l-lactate dehydrogenase, responsible for l-lactate production, and is controlled by transcription regulators SugR, LldR, and GlxR. GlxR has been shown to act as a transcriptional activator of ldhA, affecting both its promoter activity and l-lactate production.
Review
Biochemistry & Molecular Biology
Hironari Nishizawa, Mie Yamanaka, Kazuhiko Igarashi
Summary: Ferroptosis is a form of cell death triggered by intracellular peroxidation of cell membrane phospholipids. It is regulated by transcription factors NRF2 and BACH1, which control various pathways and processes involved in ferroptosis.
Article
Biochemistry & Molecular Biology
Lun Cai, Ali S. Arbab, Tae Jin Lee, Ashok Sharma, Bobby Thomas, Kazuhiko Igarashi, Raghavan Pillai Raju
Summary: The deletion of Bach1 gene improves organ function and survival in sepsis. It enhances antioxidant response, reduces oxidative stress and inflammation, preserves mitochondrial function, and regulates gene expression related to lipid metabolism. Bach1 deficiency also improves liver and lung blood flow in septic mice.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Liang Liu, Mitsuyo Matsumoto, Miki Matsui-Watanabe, Kyoko Ochiai, Bert K. K. Callens, Long Chi Nguyen, Yushi Kozuki, Miho Tanaka, Hironari Nishizawa, Kazuhiko Igarashi
Summary: The TBK1-BACH1 pathway promotes cancer cell metastasis by increasing labile iron within cells.
Article
Chemistry, Multidisciplinary
Mizuki Sawata, Hiroki Shima, Kazutaka Murayama, Toshitaka Matsui, Kazuhiko Igarashi, Kazumasa Funabashi, Kenji Ite, Kenji Kizawa, Hidenari Takahara, Masaki Unno
Summary: This study demonstrates that PAD3 has autocitrullination capacity and identifies autocitrullination sites. The number of autocitrullination sites increases with the concentration of calcium ions and reaction time, and most of the sites are located near the substrate-binding site. High calcium ion concentration may cause slight structural changes in PAD3, leading to its transformation from an active form to an inactive form.
Article
Hematology
Masatoshi Ikeda, Hiroki Kato, Hiroki Shima, Mitsuyo Matsumoto, Eijiro Furukawa, Yan Yan, Ruiqi Liao, Jian Xu, Akihiko Muto, Tohru Fujiwara, Hideo Harigae, Emery H. Bresnick, Kazuhiko Igarashi
Summary: Iron deficiency promotes mitochondrial retention in red blood cells, while heme promotes mitochondrial clearance and erythroblast differentiation. The transcription factor GATA1 regulates autophagy and induces mitophagy through a heme-dependent mechanism. This mechanism provides a molecular framework for understanding this important cell biological process.
EXPERIMENTAL HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Md Morshedul Alam, Akihiro Kishino, Eunkyu Sung, Hiroki Sekine, Takaaki Abe, Shohei Murakami, Takaaki Akaike, Hozumi Motohashi
Summary: NRF2 increases intracellular persulfides levels by upregulating the expression of cystine transporter xCT, thereby enhancing mitochondrial function.
Article
Biochemistry & Molecular Biology
Ryo Ikeda, Daisuke Noshiro, Hideaki Morishita, Shuhei Takada, Shun Kageyama, Yuko Fujioka, Tomoko Funakoshi, Satoko Komatsu-Hirota, Ritsuko Arai, Elena Ryzhii, Manabu Abe, Tomoaki Koga, Hozumi Motohashi, Mitsuyoshi Nakao, Kenji Sakimura, Arata Horii, Satoshi Waguri, Yoshinobu Ichimura, Nobuo N. Noda, Masaaki Komatsu
Summary: ULK1 is a kinase responsible for the phosphorylation of p62, which activates NRF2. p62(S351E/+) mice, with phosphorylation-mimicking mutation, exhibit NRF2 hyperactivation and growth retardation.
Article
Biochemistry & Molecular Biology
Qamarul Hafiz Zainol Abidin, Tomoaki Ida, Masanobu Morita, Tetsuro Matsunaga, Akira Nishimura, Minkyung Jung, Naim Hassan, Tsuyoshi Takata, Isao Ishii, Warren Kruger, Rui Wang, Hozumi Motohashi, Masato Tsutsui, Takaaki Akaike
Summary: Reactive sulfur species, such as cysteine hydropersulfide and glutathione persulfide, are produced abundantly in both prokaryotes and eukaryotes, including mammals. Cysteinyl-tRNA synthetase (CARS) has been identified as a new cysteine persulfide synthase (CPERS) responsible for the production of most reactive persulfides. However, the contribution of other enzymes, such as 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine beta-synthase (CBS), and cystathionine gamma-lyase (CSE), to reactive persulfide production is still debated. In this study, the authors used sulfur metabolome analysis to demonstrate that 3-MST, CBS, and CSE are not major sources of reactive persulfides in mammals, and CARS/CPERS is the principal enzyme involved.
Article
Hematology
Koki Nagai, Tetsuya Niihori, Akihiko Muto, Yoshikazu Hayashi, Taiki Abe, Kazuhiko Igarashi, Yoko Aoki
Summary: Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome caused by missense mutations in the MECOM gene. Knockin mice harboring RUSAT-associated MECOM mutations recapitulate the bone marrow dysfunction observed in RUSAT patients.
Article
Multidisciplinary Sciences
Tetsuro Matsunaga, Hirohito Sano, Katsuya Takita, Masanobu Morita, Shun Yamanaka, Tomohiro Ichikawa, Tadahisa Numakura, Tomoaki Ida, Minkyung Jung, Seiryo Ogata, Sunghyeon Yoon, Naoya Fujino, Yorihiko Kyogoku, Yusaku Sasaki, Akira Koarai, Tsutomu Tamada, Atsuhiko Toyama, Takakazu Nakabayashi, Lisa Kageyama, Shigeru Kyuwa, Kenji Inaba, Satoshi Watanabe, Peter Nagy, Tomohiro Sawa, Hiroyuki Oshiumi, Masakazu Ichinose, Mitsuhiro Yamada, Hisatoshi Sugiura, Fan-Yan Wei, Hozumi Motohashi, Takaaki Akaike
Summary: Supersulphides have diverse physiological functions and their synthesis is mediated by CARS2. They play a protective role in viral airway infections, aged lungs, and chronic lung diseases. Supersulphides can mitigate lung pathology and lethal effects in animal models, highlighting their potential as a therapeutic target.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Haruna Takeda, Shohei Murakami, Zun Liu, Tomohiro Sawa, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Hideyo Sato, Takaaki Akaike, Hiroki Sekine, Hozumi Motohashi
Summary: The excessive inflammatory response of macrophages is regulated by the metabolic alteration involving cysteine and its related metabolites. Activation of the cystine transporter xCT increases cysteine uptake by macrophages and contributes to the production of supersulfides, creating a negative feedback loop to limit excessive inflammation. Understanding the finely tuned regulation of macrophage inflammatory response by sulfur metabolism is important for disease pathogenesis and potential therapeutic strategies.
Article
Multidisciplinary Sciences
Shingo Kasamatsu, Akira Nishimura, Md. Morshedul Alam, Masanobu Morita, Kakeru Shimoda, Tetsuro Matsunaga, Minkyung Jung, Seiryo Ogata, Uladzimir Barayeu, Tomoaki Ida, Motohiro Nishida, Akiyuki Nishimura, Hozumi Motohashi, Takaaki Akaike
Summary: Research has found that abundant formation of endogenous supersulfides catalyzes S-nitrosoglutathione (GSNO) metabolism by utilizing alcohol dehydrogenase 5 (ADH5), which serves as GSNO reductase (GSNOR) and formaldehyde dehydrogenase (FDH). The C174S mutation in ADH5 significantly reduces supersulfidation and GSNOR activity but spares FDH activity. ADH5 supersulfides play a substantial role in GSNO metabolism by mediating electron transfer from aldehydes.
Article
Biology
Ritsuko Shimizu, Ikuo Hirano, Atsushi Hasegawa, Mikiko Suzuki, Akihito Otsuki, Keiko Taguchi, Fumiki Katsuoka, Akira Uruno, Norio Suzuki, Akane Yumoto, Risa Okada, Masaki Shirakawa, Dai Shiba, Satoru Takahashi, Takafumi Suzuki, Masayuki Yamamoto
Summary: Through analyzing the MHU-3 project, where Nrf2-knockout mice were sent to space for 31 days, it was discovered that mice lacking Nrf2 experienced more severe immunosuppression compared to wild-type mice. Spaceflight also induced inflammation, which was further accelerated by Nrf2 deficiency through the consumption of coagulation-fibrinolytic factors and platelets. These findings highlight the role of Nrf2 in mitigating inflammation, immunosuppression, and thrombotic microangiopathy during spaceflight.
COMMUNICATIONS BIOLOGY
(2023)
Review
Immunology
Kyoko Ochiai, Kazuhiko Igarashi
Summary: BACH2 is a transcriptional repressor that regulates gene expression in B cells, promoting antibody class switch and affinity maturation while repressing plasma-cell differentiation. Recent studies suggest that BACH2 may have diverse functions, including gene activation. Understanding these new functions could provide insights into preventing human immune deficiencies.
INTERNATIONAL IMMUNOLOGY
(2023)
Article
Nutrition & Dietetics
Kotaro Kaneko, Yoichi Miyamoto, Tomoaki Ida, Masanobu Morita, Kentaro Yoshimura, Kei Nagasaki, Kazuki Toba, Risa Sugisaki, Hozumi Motohashi, Takaaki Akaike, Daichi Chikazu, Ryutaro Kamijo
Summary: 8-nitro-cGMP has been found to be a negative regulator of osteoblastic differentiation in bone remodeling.
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2022)