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Article ; Online: A Window to the Potassium World. The Evidence of Potassium Energetics in the Mitochondria and Identity of the Mitochondrial ATP-Dependent K

Zorov, Dmitry B

2022 Volume 87, Issue 8, Page(s) 683–688

Abstract: The conclusions made in the three papers published in Function by Juhaszova et al. [Function, 3, 2022, zqab065, zqac001, zqac018], can be seen as a breakthrough in bioenergetics and mitochondrial medicine. For more than half a century, it has been ... ...

Abstract	The conclusions made in the three papers published in Function by Juhaszova et al. [Function, 3, 2022, zqab065, zqac001, zqac018], can be seen as a breakthrough in bioenergetics and mitochondrial medicine. For more than half a century, it has been believed that mitochondrial energetics is solely protonic and is based on the generation of electrochemical potential of hydrogen ions across the inner mitochondrial membrane upon oxidation of respiratory substrates, resulting in the generation of ATP via reverse transport of protons through the ATP synthase complex. Juhaszova et al. demonstrated that ATP synthase transfers not only protons, but also potassium ions, with the generation of ATP. This mechanism seems logical, given the fact that in eukaryotic cells, the concentration of potassium ions is several million times higher than the concentration of protons. The transport of K+ through the ATP synthase was enhanced by the activators of mitochondrial ATP-dependent K+ channel (
MeSH term(s)	Adenosine Triphosphate ; Mitochondria/metabolism ; Potassium/metabolism ; Potassium Channels/physiology ; Protons ; Water
Chemical Substances	Potassium Channels ; Protons ; Water (059QF0KO0R) ; Adenosine Triphosphate (8L70Q75FXE) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2022-09-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297922080016
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Article ; Online: Isn't It Time for Establishing Mitochondrial Nomenclature Breaking Mitochondrial Paradigm?

Zorov, Dmitry B / Andrianova, Nadezda V / Babenko, Valentina A / Zorova, Ljubava D / Zorov, Savva D / Pevzner, Irina B / Sukhikh, Gennady T / Silachev, Denis N

Biochemistry. Biokhimiia

2023 Volume 87, Issue 12, Page(s) 1487–1497

Abstract: In this work, we decided to initiate a discussion concerning heterogeneity of mitochondria, suggesting that it is time to build classification of mitochondria, like the one that exists for their progenitors, α-proteobacteria, proposing possible ... ...

Abstract	In this work, we decided to initiate a discussion concerning heterogeneity of mitochondria, suggesting that it is time to build classification of mitochondria, like the one that exists for their progenitors, α-proteobacteria, proposing possible separation of mitochondrial strains and maybe species. We continue to adhere to the general line that mitochondria are friends and foes: on the one hand, they provide the cell and organism with the necessary energy and signaling molecules, and, on the other hand, participate in destruction of the cell and the organism. Current understanding that the activity of mitochondria is not only limited to energy production, but also that these alternative non-energetic functions are unique and irreplaceable in the cell, allowed us to speak about the strong subordination of the entire cellular metabolism to characteristic functional manifestations of mitochondria. Mitochondria are capable of producing not only ATP, but also iron-sulfur clusters, steroid hormones, heme, reactive oxygen and nitrogen species, participate in thermogenesis, regulate cell death, proliferation and differentiation, participate in detoxification, etc. They are a mandatory attribute of eukaryotic cells, and, so far, no eukaryotic cells performing a non-parasitic or non-symbiotic life style have been found that lack mitochondria. We believe that the structural-functional intracellular, intercellular, inter-organ, and interspecific diversity of mitochondria is large enough to provide grounds for creating a mitochondrial nomenclature. The arguments for this are given in this analytical work.
MeSH term(s)	Humans ; Mitochondria/metabolism ; Eukaryotic Cells/metabolism ; Cell Differentiation ; Oxygen/metabolism ; Reactive Oxygen Species/metabolism
Chemical Substances	Oxygen (S88TT14065) ; Reactive Oxygen Species
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297922120069
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Article ; Online: Mitocentricity.

Zorov, Dmitry B / Abramicheva, Polina A / Andrianova, Nadezda V / Babenko, Valentina A / Zorova, Ljubava D / Zorov, Savva D / Pevzner, Irina B / Popkov, Vasily A / Semenovich, Dmitry S / Yakupova, Elmira I / Silachev, Denis N / Plotnikov, Egor Y / Sukhikh, Gennady T

Biochemistry. Biokhimiia

2024 Volume 89, Issue 2, Page(s) 223–240

Abstract: Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more prevalent than studies of other cellular structures. In this analytical review, ... ...

Abstract	Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more prevalent than studies of other cellular structures. In this analytical review, mitochondria are conditionally placed in a certain cellular center, which is responsible for both energy production and other non-energetic functions, without which the existence of not only the eukaryotic cell itself, but also the entire organism is impossible. Taking into account the high multifunctionality of mitochondria, such a fundamentally new scheme of cell functioning organization, including mitochondrial management of processes that determine cell survival and death, may be justified. Considering that this issue is dedicated to the memory of V. P. Skulachev, who can be called mitocentric, due to the history of his scientific activity almost entirely aimed at studying mitochondria, this work examines those aspects of mitochondrial functioning that were directly or indirectly the focus of attention of this outstanding scientist. We list all possible known mitochondrial functions, including membrane potential generation, synthesis of Fe-S clusters, steroid hormones, heme, fatty acids, and CO2. Special attention is paid to the participation of mitochondria in the formation and transport of water, as a powerful biochemical cellular and mitochondrial regulator. The history of research on reactive oxygen species that generate mitochondria is subject to significant analysis. In the section "Mitochondria in the center of death", special emphasis is placed on the analysis of what role and how mitochondria can play and determine the program of death of an organism (phenoptosis) and the contribution made to these studies by V. P. Skulachev.
MeSH term(s)	Mitochondria/metabolism ; Reactive Oxygen Species/metabolism
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297924020044
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Article: Targeting Mitochondria for Cancer Treatment.

Zorova, Ljubava D / Abramicheva, Polina A / Andrianova, Nadezda V / Babenko, Valentina A / Zorov, Savva D / Pevzner, Irina B / Popkov, Vasily A / Semenovich, Dmitry S / Yakupova, Elmira I / Silachev, Denis N / Plotnikov, Egor Y / Sukhikh, Gennady T / Zorov, Dmitry B

Pharmaceutics

2024 Volume 16, Issue 4

Abstract: There is an increasing accumulation of data on the exceptional importance of mitochondria in the occurrence and treatment of cancer, and in all lines of evidence for such participation, there are both energetic and non-bioenergetic functional features of ...

Abstract	There is an increasing accumulation of data on the exceptional importance of mitochondria in the occurrence and treatment of cancer, and in all lines of evidence for such participation, there are both energetic and non-bioenergetic functional features of mitochondria. This analytical review examines three specific features of adaptive mitochondrial changes in several malignant tumors. The first feature is characteristic of solid tumors, whose cells are forced to rebuild their energetics due to the absence of oxygen, namely, to activate the fumarate reductase pathway instead of the traditional succinate oxidase pathway that exists in aerobic conditions. For such a restructuring, the presence of a low-potential quinone is necessary, which cannot ensure the conventional conversion of succinate into fumarate but rather enables the reverse reaction, that is, the conversion of fumarate into succinate. In this scenario, complex I becomes the only generator of energy in mitochondria. The second feature is the increased proliferation in aggressive tumors of the so-called mitochondrial (peripheral) benzodiazepine receptor, also called translocator protein (TSPO) residing in the outer mitochondrial membrane, the function of which in oncogenic transformation stays mysterious. The third feature of tumor cells is the enhanced retention of certain molecules, in particular mitochondrially directed cations similar to rhodamine 123, which allows for the selective accumulation of anticancer drugs in mitochondria. These three features of mitochondria can be targets for the development of an anti-cancer strategy.
Language	English
Publishing date	2024-03-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics16040444
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Article: Pros and Cons of Use of Mitochondria-Targeted Antioxidants.

Plotnikov, Egor Y / Zorov, Dmitry B

Antioxidants (Basel, Switzerland)

2019 Volume 8, Issue 8

Abstract: Mitochondrial targeting is a novel strategy, which addresses pathologies originating from mitochondrial dysfunction. Here, one of the most potent therapeutics arises from the group of mitochondria-targeted antioxidants, which specifically quench ... ...

Abstract	Mitochondrial targeting is a novel strategy, which addresses pathologies originating from mitochondrial dysfunction. Here, one of the most potent therapeutics arises from the group of mitochondria-targeted antioxidants, which specifically quench mitochondrial reactive oxygen species (ROS). They show very high efficacy in the treatment of a diverse array of pathologies encountered in this Special Issue of
Language	English
Publishing date	2019-08-17
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox8080316
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Article ; Online: Bioenergetics of the Fibrosis.

Yakupova, Elmira I / Zorov, Dmitry B / Plotnikov, Egor Y

Biochemistry. Biokhimiia

2021 Volume 86, Issue 12, Page(s) 1599–1606

Abstract: It is known that the development of fibrosis is associated with many diseases, being both a cause and effect of the damage to organs and tissues. Replacement of functional tissue with a scar can lead to organ dysfunction, which is often a life- ... ...

Abstract	It is known that the development of fibrosis is associated with many diseases, being both a cause and effect of the damage to organs and tissues. Replacement of functional tissue with a scar can lead to organ dysfunction, which is often a life-threatening condition. The development of effective approaches for the prevention or treatment of fibrosis requires an in-depth understanding of all aspects of its pathogenesis, from epithelial-mesenchymal transformation to fibroblast proliferation. Fibrosis can be induced by trauma, ischemic injury, inflammation, and many other pathological states accompanied by repeated cycles of tissue damage and repair. Energy metabolism is the basis of functioning of all cells in an organism and its disruptions are associated with the development of different diseases, hence, it could be a target for the therapy of such pathological processes as ischemia/reperfusion, epilepsy, diabetes, cancer, and neurological disorders. The emergence of fibrosis is also associated with the changes in cell bioenergetics. In this work, we analyzed the changes in the energy metabolism that occur with the progression of fibrosis and evaluated the possibility of affecting energetics as target in the anti-fibrotic approach.
MeSH term(s)	Animals ; Energy Metabolism ; Epithelial-Mesenchymal Transition ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Fibrosis ; Humans
Language	English
Publishing date	2021-12-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297921120099
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Article ; Online: Setting the Record Straight: A New Twist on the Chemiosmotic Mechanism of Oxidative Phosphorylation.

Juhaszova, Magdalena / Kobrinsky, Evgeny / Zorov, Dmitry B / Aon, Miguel A / Cortassa, Sonia / Sollott, Steven J

Function (Oxford, England)

2022 Volume 3, Issue 3, Page(s) zqac018

MeSH term(s)	Oxidative Phosphorylation ; Proton-Motive Force ; Mitochondria/metabolism ; Adenosine Triphosphate/metabolism ; Biochemical Phenomena ; Nitric Oxide Synthase/metabolism
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE) ; Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2022-04-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Comment
ISSN	2633-8823
ISSN (online)	2633-8823
DOI	10.1093/function/zqac018
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Article ; Online: Mitochondrial Network: Electric Cable and More.

Abramicheva, Polina A / Andrianova, Nadezda V / Babenko, Valentina A / Zorova, Ljubava D / Zorov, Savva D / Pevzner, Irina B / Popkov, Vasily A / Semenovich, Dmitry S / Yakupova, Elmira I / Silachev, Denis N / Plotnikov, Egor Y / Sukhikh, Gennady T / Zorov, Dmitry B

Biochemistry. Biokhimiia

2023 Volume 88, Issue 10, Page(s) 1596–1607

Abstract: Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the ... ...

Abstract	Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the oxidation energy of respiratory substrates is largely stored in the form of an electrical potential difference on the inner membrane of mitochondria. The theory of the functioning of extended mitochondrial structures as intracellular electrical wires suggests that mitochondria provide the fastest delivery of electrical energy through the cellular volume, followed by the use of this energy for the synthesis of ATP, thereby accelerating the process of ATP delivery compared to the rather slow diffusion of ATP in the cell. This analytical review gives the history of the cable theory, lists unsolved critical problems, describes the restructuring of the mitochondrial network and the role of oxidative stress in this process. In addition to the already proven functioning of extended mitochondrial structures as electrical cables, a number of additional functions are proposed, in particular, the hypothesis is put forth that mitochondrial networks maintain the redox potential in the cellular volume, which may vary depending on the physiological state, as a result of changes in the three-dimensional organization of the mitochondrial network (fragmentation/fission-fusion). A number of pathologies accompanied by a violation of the redox status and the participation of mitochondria in them are considered.
MeSH term(s)	Mitochondria/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Adenosine Triphosphate/metabolism
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2023-12-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297923100140
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Article ; Online: Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110.

Brezgunova, Anna A / Andrianova, Nadezda V / Saidova, Aleena A / Potashnikova, Daria M / Abramicheva, Polina A / Manskikh, Vasily N / Mariasina, Sofia S / Pevzner, Irina B / Zorova, Ljubava D / Manzhulo, Igor V / Zorov, Dmitry B / Plotnikov, Egor Y

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to ...

Abstract	The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to exert anti-inflammatory and neurogenic properties. The aim of this study was to investigate the anti-inflammatory effect of synaptamide in ischemic AKI. For this purpose, we analyzed the expression of inflammatory mediators and the infiltration of different leukocyte populations into the kidney after injury, evaluated the expression of the putative synaptamide receptor G-protein-coupled receptor 110 (GPR110), and isolated a population of CD11b/c
MeSH term(s)	Animals ; Rats ; Acute Kidney Injury/drug therapy ; Acute Kidney Injury/metabolism ; Anti-Inflammatory Agents/metabolism ; Ethanolamines ; Interleukins/metabolism ; Kidney/metabolism ; Receptors, G-Protein-Coupled/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Reperfusion Injury/drug therapy ; Reperfusion Injury/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Ethanolamines ; Interleukins ; Receptors, G-Protein-Coupled ; synaptamide
Language	English
Publishing date	2024-01-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25031500
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Article ; Online: Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury.

Andrianova, Nadezda V / Brezgunova, Anna A / Buyan, Marina I / Makievskaya, Ciara I / Buyan, Andrey I / Cherkesova, Kseniia S / Pevzner, Irina B / Zorova, Ljubava D / Zorov, Dmitry B / Plotnikov, Egor Y / Popkov, Vasily A

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of ... ...

Abstract	The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.
MeSH term(s)	Humans ; Rats ; Male ; Female ; Animals ; Progesterone/adverse effects ; Estradiol/adverse effects ; Kidney/pathology ; Ischemia/complications ; Reperfusion Injury/pathology ; Acute Kidney Injury/etiology
Chemical Substances	Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2024-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063155
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