Article
Cardiac & Cardiovascular Systems
Hector Chapoy Villanueva, Jae Hwi Sung, Jackie A. Stevens, Michael J. Zhang, Peyton M. Nelson, Lalitha S. Denduluri, Feng Feng, Timothy D. O'Connell, DeWayne Townsend, Julia C. Liu
Summary: Transport of Ca2+ into mitochondria through the mitochondrial Ca2+ uniporter complex is essential for ATP production, but excessive Ca2+ can be detrimental. Short-term deletion of the regulatory protein EMRE in the heart resulted in impaired Ca2+ uptake, attenuated ATP production, and improved cardiac function in an I/R model. However, long-term EMRE loss led to similar impairment in Ca2+ handling and function, but loss of protection against I/R injury. These findings suggest that long-term absence of EMRE restores susceptibility to I/R, despite impaired bioenergetic response.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Article
Cell Biology
Courtney E. Petersen, Junhui Sun, Kavisha Silva, Anna Kosmach, Robert S. Balaban, Elizabeth Murphy
Summary: The regulation of cell death by mitochondrial calcium overload and the potential role of mitochondrial calcium uniporter (MCU) in preventing cell death during ischemia/reperfusion are investigated using ex-vivo-perfused mouse hearts. It is found that inhibition of MCU reduces mitochondrial calcium accumulation during ischemia, but there is still an increase in mitochondrial calcium, suggesting that mitochondrial calcium overload is not solely dependent on MCU.
Article
Biochemistry & Molecular Biology
Plinio Bezerra Palacio, Geovanna Carvalho de Freitas Soares, Gabriella Moreira Bezerra Lima, Pedro Lourenzo Oliveira Cunha, Anna Lidia Nunes Varela, Heberty Tarso Facundo
Summary: This study investigates the molecular and physiological mechanisms of activators (GTP) and inhibitors (ATP) in the activity of mitoKATP channels. The findings demonstrate that ATP inhibits mitoKATP activity, while GTP reverses this inhibition in a dose-dependent manner. Both nucleotides bind to mitoSUR and competitively affect its function. These results are important for further understanding the role of GTP and ATP in cardioprotection.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Review
Biochemistry & Molecular Biology
Yevheniia Kravenska, Vanessa Checchetto, Ildiko Szabo
Summary: Potassium ions can enter and exit mitochondria through various channels in the outer and inner membranes, with the ATP-dependent potassium channel being the most studied and playing a crucial role in protecting cells against ischemic and neuronal damage.
Article
Pharmacology & Pharmacy
Plinio Bezerra Palacio, Aline Maria Brito Lucas, Joana Varlla de Lacerda Alexandre, Pedro Lourenzo Oliveira Cunha, Yuana Ivia Ponte Viana, Amanda Cabral Albuquerque, Anna Lidia Nunes Varela, Heberty Tarso Facundo
Summary: The study reveals competitive binding of glibenclamide and diazoxide at mitoSUR, with the cyclohexylurea portion of glibenclamide being essential for mitoKATP inhibition. IMP-A does not inhibit diazoxide-induced cardioprotection, but glibenclamide effectively inhibits it. This research provides valuable insights into the pharmacological and biochemical aspects of mitoKATP activation and cardioprotection, potentially leading to new therapeutic strategies for ischemia-reperfusion injury.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Environmental Sciences
Elena A. Belyaeva
Summary: Heavy metals are harmful environmental pollutants with unknown mechanisms of cytotoxicity. This study investigated the role of mitochondrial ATP-sensitive potassium channel (mK(ATP)) in hepatotoxicity caused by heavy metals. The effects of mK(ATP) modulators and activators on respiration and membrane permeability were studied using isolated liver mitochondria. It was found that mK(ATP) modulators affect Cd2+- and/or Cu2+-induced alterations in mitochondrial swelling and respiration rates. In addition, the simultaneous use of Cu2+ and diazoxide led to increased production of reactive oxygen species and cell death. The relationships between mK(ATP) and mitochondrial electron transport chain components were discussed.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Physiology
Masaki Yamanaka, Yoshifuru Tamura, Emiko Kuribayashi-Okuma, Shunya Uchida, Shigeru Shibata
Summary: Our study demonstrates that stimulating Mit(KATP) with nicorandil can reduce proteinuria by attenuating podocyte injury in PAN nephrosis, restoring mitochondrial antioxidative capacity, possibly through mitochondrial Ca2+ uniporter modulation. These findings suggest that Mit(KATP) may represent a novel target for podocyte injury and nephrotic syndrome.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Shiru Bai, Xuechao Wang, Haibo Wu, Tianlei Chen, Xinning Li, Lina Zhang, Xiangming Li, Lu Er, Rongpin Du
Summary: The study demonstrated that anisodamine could protect against myocardial ischemia/reperfusion injury by improving mitochondrial energy metabolism, reducing oxidative stress, and stabilizing mitochondrial membrane potential. The opening of mitoK ATP may play a crucial role in the cardioprotective effects of anisodamine.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Multidisciplinary Sciences
Wenping Wu, Jimin Zheng, Zongchao Jia
Summary: The mitochondrial uniporter is a Ca2+-selective ion-conducting channel in the inner mitochondrial membrane composed of MCU, MCUb, EMRE, MICU1, and MICU2. Recent structural studies have provided insights into the component structures and their spatial relationship, contributing to a better understanding of mitochondrial Ca2+ uptake and regulation. Further research in this area could lead to advancements in studying mitochondrial Ca2+ permeation and related diseases.
Review
Pharmacology & Pharmacy
Umberto De Marchi, Silvia Fernandez-Martinez, Sergio de la Fuente, Andreas Wiederkehr, Jaime Santo-Domingo
Summary: Pancreatic beta-cells play a central role in regulating glucose homeostasis, with mitochondria playing a crucial role in linking nutrient metabolism to insulin secretion. Mitochondria, as double-membrane organelles with various channels, regulate energy production, signaling, and cell death within beta-cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Macarena Rodriguez-Prados, Elena Berezhnaya, Maria Teresa Castromonte, Sergio L. Menezes-Filho, Melanie Paillard, Gyorgy Hajnoczky
Summary: Mitochondrial Ca2+ uptake is regulated by the mtCU complex, which consists of MCU, EMRE, and MICU1/2/3 subunits. MICU1 has been proposed to physically block the mtCU pore and regulate Ca2+ flux at different cytoplasmic [Ca2+]. We studied the mtCU in divalent-free conditions and found that MICU1 restricts Na+ influx, but some mtCU channels appear to lack MICU1-dependent gating in cells with high endogenous MICU1 expression. The rearrangement of mtCU and loss of MICU1 during mitoplast preparation might have affected previous studies in divalent-free conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
M. A. Neginskaya, E. V. Pavlov, S-S. Sheu
Summary: The mitochondrial permeability transition pore (mPTP) is a channel that increases the permeability of the mitochondrial inner membrane when open, leading to cell death in diseases such as hypoxic injuries, neurodegeneration, and diabetes. Recent discoveries show that mPTP exhibits complex behavior and multiple molecular identities.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Review
Biochemistry & Molecular Biology
Jiho Yoo
Summary: Mitochondria, organelles responsible for various cellular functions, uptake Ca2+ ions through the MCU holo-complex. The protein structure of the MCU holo-complex has recently been identified, providing insights into the uptake and regulation mechanisms.
Article
Multidisciplinary Sciences
Chen Zhao, Roderick MacKinnon
Summary: K-ATP channels act as metabolic sensors translating ATP/ADP balance to membrane excitability. The structure of human pancreatic K-ATP reveals an open pore, coordinated structural changes within the ATP-binding site and channel gate in Kir, as well as conformational changes in SUR. The pancreatic hK(ATP) exhibits a unique PIP2-independent opening property.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Ju Tang, Weixia Duan, Ping Deng, Huijuan Li, Cong Liu, Yu Duan, Min Feng, Shangcheng Xu
Summary: Cadmium exposure slows down the rapid movement of mitochondria in neurons, leading to abnormal distribution and excessive fragmentation of mitochondria, ultimately causing mitochondrial membrane potential loss and neuronal damage. Chelating overloaded cytosolic calcium is a promising strategy to prevent cadmium-induced neurotoxicity.
Article
Pharmacology & Pharmacy
Akiteru Kojima, Akio Matsumoto, Hirofumi Nishida, Yoshie Reien, Kazumi Iwata, Takeshi Shirayama, Chihiro Yabe-Nishimura, Haruaki Nakaya
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2015)
Article
Pharmacology & Pharmacy
Yasuhiro Watanabe, Akio Matsumoto, Takashi Miki, Susumu Seino, Naohiko Anzai, Haruaki Nakaya
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2017)
Article
Microbiology
Kimitoshi Ichimura, Takeshi Shimizu, Akio Matsumoto, Shinichiro Hirai, Eiji Yokoyama, Hiroki Takeuchi, Kinnosuke Yahiro, Masatoshi Noda
Article
Biochemistry & Molecular Biology
Hiroaki Korekane, Tomoko Hasegawa, Akio Matsumoto, Noriaki Kinoshita, Eiji Miyoshi, Naoyuki Taniguchi
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2012)
Article
Biochemistry & Molecular Biology
Congxiao Gao, Toshitaka Maeno, Fumi Ota, Manabu Ueno, Hiroaki Korekane, Shinji Takamatsu, Ken Shirato, Akio Matsumoto, Satoshi Kobayashi, Keiichi Yoshida, Shinobu Kitazume, Kazuaki Ohtsubo, Tomoko Betsuyaku, Naoyuki Taniguchi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Hiroaki Korekane, Jong Yi Park, Akio Matsumoto, Kazuki Nakajima, Shinji Takamatsu, Kazuaki Ohtsubo, Yasuhide Miyamoto, Shinya Hanashima, Kenji Kanekiyo, Shinobu Kitazume, Yoshiki Yamaguchi, Ichiro Matsuo, Naoyuki Taniguchi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Pharmacology & Pharmacy
Atsushi Nishida, Taichi Takizawa, Akio Matsumoto, Takashi Miki, Susumu Seino, Haruaki Nakaya
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2011)
Article
Pharmacology & Pharmacy
Kazumasa Suzuki, Akio Matsumoto, Hirofumi Nishida, Yoshie Reien, Hiroo Maruyama, Haruaki Nakaya
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2014)
Article
Biochemistry & Molecular Biology
Takeshi Shimizu, Hiroyasu Tsutsuki, Akio Matsumoto, Haruaki Nakaya, Masatoshi Noda
MOLECULAR MICROBIOLOGY
(2012)
Article
Biochemistry & Molecular Biology
Akio Matsumoto, Andrew J. Gow
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2011)
Article
Multidisciplinary Sciences
Kenji Sugawara, Kohei Honda, Yoshie Reien, Norihide Yokoi, Chihiro Seki, Harumi Takahashi, Kohtaro Minami, Ichiro Mori, Akio Matsumoto, Haruaki Nakaya, Susumu Seino
Article
Multidisciplinary Sciences
Akio Matsumoto, Megumi Yamafuji, Tomoko Tachibana, Yusaku Nakabeppu, Mami Noda, Haruaki Nakaya
SCIENTIFIC REPORTS
(2013)
Article
Multidisciplinary Sciences
Yoshitami Sanayama, Akio Matsumoto, Naoki Shimojo, Yoichi Kohno, Haruaki Nakaya
SCIENTIFIC REPORTS
(2014)
Article
Multidisciplinary Sciences
Yasuhiro Watanabe, Takashi Kishimoto, Takashi Miki, Susumu Seino, Haruaki Nakaya, Akio Matsumoto
SCIENTIFIC REPORTS
(2018)
Article
Microbiology
Takeshi Shimizu, Manami Onuki, Shin Suzuki, Shinichiro Hirai, Eiji Yokoyama, Akio Matsumoto, Takashi Hamabata
Summary: Stx1 production in EHEC is affected by oxygen concentration, with higher levels produced under aerobic conditions. The Fe2+-responsive transcription factor Fur plays a key role in this regulation by influencing DNA binding and ultimately Stx1 production.