Article
Biology
Giampaolo Morciano, Natalia Naumova, Piotr Koprowski, Sara Valente, Vilma A. Sardao, Yaiza Potes, Alessandro Rimessi, Mariusz R. Wieckowski, Paulo J. Oliveira
Summary: This review summarizes the intriguing phenomenon of the mitochondrial permeability transition pore (mPTP) in cell biology. Despite almost 50 years of research, the mechanisms of mPTP are still not definitively understood. From initially being considered an in vitro artifact to now being recognized for its physiological and pathological implications, the journey of mPTP research has been long and complex.
BIOLOGICAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Vincenzo Algieri, Cristina Algieri, Loredana Maiuolo, Antonio De Nino, Alessandra Pagliarani, Matteo Antonio Tallarida, Fabiana Trombetti, Salvatore Nesci
Summary: The study identified two 1,5-disubstituted 1,2,3-triazole derivatives that inhibit the opening of the mitochondrial permeability transition pore without affecting mitochondrial respiration.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Review
Cell Biology
Rene Endlicher, Zdenek Drahota, Katerina Stefkova, Zuzana Cervinkova, Otto Kucera
Summary: The mitochondrial permeability transition pore (MPTP) is a calcium-dependent, ion non-selective membrane pore with various functions. Its reversible opening protects cells from oxidative damage and allows Ca2+ ions efflux, while its irreversible opening leads to cell death. The sensitivity of the pore to Ca2+ ions changes with aging and plays a key role in disease pathogenesis.
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)
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
Biochemistry & Molecular Biology
Salvatore Nesci
Summary: The F1FO-ATPase is an important enzyme that plays a crucial role in ATP synthesis and hydrolysis. It interacts with Ca2+ to modulate its biological function and is involved in the formation of mitochondrial permeability transition pore. Understanding the role of Ca2+ in F1FO-ATPase can provide insights into the molecular mechanism of mPTP.
Article
Biochemistry & Molecular Biology
Salvatore Nesci
Summary: The F1FO-ATPase uses Mg2+ as a natural cofactor and can perform both ATP synthesis and hydrolysis. Under different physiological or pathological conditions, Ca2+ can interact with the enzyme and modify its biological role. Ca2+ binding sites have been identified in two regions of the enzyme complex: the F-1 catalytic sites and the membrane-embedded domain FO. When activated by Ca2+, the enzyme primarily functions as an H+-translocating F1FO-ATP(hydrol)ase with a monofunctional activity, leading to the formation of the mitochondrial permeability transition pore (mPTP) phenomenon.
Article
Food Science & Technology
Paulina Patalas-Krawczyk, Dominika Malinska, Jaroslaw Walczak, Gilles Kratzer, Monika Prill, Bernadeta Michalska, Karolina Drabik, Bjorn Titz, Yvan Eb-Levadoux, Thomas Schneider, Jedrzej Szymanski, Julia Hoeng, Manuel C. Peitsch, Jerzy Duszynski, Joanna Szczepanowska, Marco Van der Toorn, Carole Mathis, Mariusz R. Wieckowski
Summary: Mitochondria play an important role in responding to stress factors, and alkaloids from tobacco plants such as nicotine, anatabine, and anabasine can modulate mitochondrial activities differently in mouse brain and liver tissues. These alkaloids affect mitochondrial bioenergetics parameters, including oxygen consumption and swelling rates, with potential toxic effects observed in liver mitochondria. The observed effects are likely independent of nicotinic acetylcholine receptors based on quantitative proteomic analysis.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Cristina Algieri, Fabiana Trombetti, Alessandra Pagliarani, Micaela Fabbri, Salvatore Nesci
Summary: The study found that gadolinium has a strong inhibitory effect on both the mitochondrial Ca2+-activated F1FO-ATPase and the PTP, strengthening the link between the two. This provides new insights into the biological effects of Gd3+.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Physiology
Sehwan Jang, Xavier R. Chapa-Dubocq, Silvia Fossati, Sabzali Javadov
Summary: The study compared the quantification of mitochondrial CRC in isolated cell mitochondria and permeabilized cells, demonstrating higher CRC in saponin-permeabilized cells. This indicates that quantifying mitochondrial CRC in cultured cells permeabilized by saponin has more advantages compared to isolated mitochondria.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Xavier R. Chapa-Dubocq, Keishla M. Rodriguez-Graciani, Nelson Escobales, Sabzali Javadov
Summary: Mitochondria, known as the powerhouse of the cell, regulate various cellular processes including ion homeostasis, energy production, and cell death. The inner mitochondrial membrane (IMM) plays a critical role in controlling mitochondrial metabolism and function. The volume of the mitochondrial matrix, regulated by ion transport mechanisms, influences IMM remodeling and can affect mitochondrial respiration and cell survival. Despite extensive research, the mechanisms underlying changes in matrix volume and IMM remodeling in response to energy and oxidative stressors remain poorly understood. This review summarizes previous studies and discusses the interplay between matrix volume regulation and IMM remodeling.
Review
Cell Biology
Artyom Y. Baev, Andrey Y. Vinokurov, Irina N. Novikova, Viktor V. Dremin, Elena V. Potapova, Andrey Y. Abramov
Summary: Neurodegenerative disorders are devastating diseases characterized by the loss of neurons in specific brain regions. Recent research has identified genes, toxins, and risk factors associated with these diseases, and has found similarities in the involvement of mitochondria, oxidative stress, and abnormal calcium signaling in neurons and astrocytes.
Article
Biochemistry & Molecular Biology
Miguel Olivas-Aguirre, Liliana Torres-Lopez, Zeferino Gomez-Sandoval, Kathya Villatoro-Gomez, Igor Pottosin, Oxana Dobrovinskaya
Summary: The study demonstrated a synergistic cytotoxic effect of TAM and CBD against T-ALL cells. TAM targets CypD to inhibit mPTP formation, sensitizing T-ALL to CBD by altering mitochondrial Ca2+ homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Galina D. Mironova, Evgeny V. Pavlov
Summary: Mitochondrial permeability transition (mPT) is a sharp increase in the permeability of the mitochondrial inner membrane under Ca2+ and ROS stress, and can occur through opening protein channels or lipid pores. The formation of palmitate/Ca2+ induced pores may play a protective role against calcium and ROS toxicity.
Review
Biochemistry & Molecular Biology
Hagai Rottenberg
Summary: It is widely reported that the mitochondrial membrane potential, increment ψm, is reduced in aging animals. It was recently suggested that the lower increment ψm in aged animals modulates mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased increment ψm in C. elegans increased lifespan. The activation of the voltage-gated mitochondrial permeability transition pore (mPTP) is the main cause of the increase in depolarized mitochondria in aged cells, inhibiting oxidative phosphorylation, releasing calcium and mROS, and depleting NAD(+), thereby accelerating degenerative diseases and aging. The reported lifespan extension by artificially generated increment ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Ta-Ming Liu, Jennifer A. Woyach, Yiming Zhong, Arletta Lozanski, Gerard Lozanski, Shuai Dong, Ethan Strattan, Amy Lehman, Xiaoli Zhang, Jeffrey A. Jones, Joseph Flynn, Leslie A. Andritsos, Kami Maddocks, Samantha M. Jaglowski, Kristie A. Blum, John C. Byrd, Jason A. Dubovsky, Amy J. Johnson
Article
Biochemistry & Molecular Biology
Yiming Zhong, Shuai Dong, Ethan Strattan, Li Ren, Jonathan P. Butchar, Kelsey Thornton, Anjali Mishra, Pierluigi Porcu, J. Michael Bradshaw, Angelina Bisconte, Timothy D. Owens, Erik Verner, Ken A. Brameld, Jens Oliver Funk, Ronald J. Hill, Amy J. Johnson, Jason A. Dubovsky
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Meeting Abstract
Oncology
Amy J. Johnson, Shuai Dong, Daphne Guinn, Jason A. Dubovsky, Yiming Zhong, Amy Lehman, Jeff Kutok, Jennifer A. Woyach, John C. Byrd
MOLECULAR CANCER THERAPEUTICS
(2015)
Editorial Material
Oncology
Shuai Dong, John C. Byrd
Article
Hematology
Shuai Dong, Daphne Guinn, Jason A. Dubovsky, Yiming Zhong, Amy Lehman, Jeffery Kutok, Jennifer A. Woyach, John C. Byrd, Amy J. Johnson
Article
Medicine, Research & Experimental
Shuai Dong, Bonnie K. Harrington, Eileen Y. Hu, Joseph T. Greene, Amy M. Lehman, Minh Tran, Ronni L. Wasmuth, Meixiao Long, Natarajan Muthusamy, Jennifer R. Brown, Amy J. Johnson, John C. Byrd
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Editorial Material
Medicine, Research & Experimental
Shuai Dong, Irene M. Ghobrial
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Hematology
Ishwarya Murali, Siddha Kasar, Aishath Naeem, Svitlana Tyekucheva, Jasneet K. Khalsa, Emily M. Thrash, Gilad Itchaki, Dimitri Livitz, Ignaty Leshchiner, Shuai Dong, Stacey M. Fernandes, Gad Getz, Amy Johnson, Jennifer R. Brown
Summary: Resistance to PI3K delta inhibitors in CLL is associated with baseline activating mutations and activation of the MAPK/ERK pathway, suggesting a rationale for combination therapy with PI3K delta and ERK inhibitors.
