• BMB Reports
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• v.55 no.11
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• pp.528-534
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• 2022

Mitochondria are cellular organelles that perform various functions within cells. They are responsible for ATP production, cell-signal regulation, autophagy, and cell apoptosis. Because the mitochondrial proteins that perform these functions need Ca²⁺ ions for their activity, mitochondria have ion channels to selectively uptake Ca²⁺ ions from the cytoplasm. The ion channel known to play the most important role in the Ca²⁺ uptake in mitochondria is the mitochondrial calcium uniporter (MCU) holo-complex located in the inner mitochondrial membrane (IMM). This ion channel complex exists in the form of a complex consisting of the pore-forming protein through which the Ca²⁺ ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca²⁺ uptake by the MCU holo-complex. Studies of this MCU holo-complex have long been conducted, but we didn't know in detail how mitochondria uptake Ca²⁺ ions through this ion channel complex or how the activity of this ion channel complex is regulated. Recently, the protein structure of the MCU holo-complex was identified, enabling the mechanism of Ca²⁺ uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of action of the MCU holo-complex at the molecular level based on the Cryo-EM structure of the MCU holo-complex to help understand how mitochondria uptake the necessary Ca²⁺ ions through the MCU holo-complex and how these Ca²⁺ uptake mechanisms are regulated.

• Journal of Biomedical Engineering Research
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• v.30 no.5
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• pp.355-361
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• 2009

Mitochondria play a key role in maintaining life by producing ATP and heat. Recent researches have demonstrated that degenerative diseases such as heart failure, obesity/diabetes, cardiovascular disease, and psychiatric diseases are accompanied by mitochondria dysfunction. In this sense, mitochondria medicine considers the significance of mitochondria in human pathology and tries to explain degenerative diseases as a fatal consequence of mitochondria dysfunction. Here, I introduce the fundamentals of mitochondria physiology and present examples showing the relationship between mitochondria dysfunction and chronic complex diseases. Although mitochondria medicine uses a molecular biological approach predominantly, a biomedical engineering approach might play a critical role in unveiling the complexity of mitochondria medicine and in its application to the diagnosis and treatment of chronic diseases. Thus, I also briefly review the prospects of research using biomedical engineering methods.

• Animal cells and systems
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• v.14 no.2
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• pp.91-98
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• 2010

Male rats were given a single injection of iron, and temporal changes in iron content and iron-induced effects were examined in heart cellular fractions. Over a period of 72 h, the contents of total and labile iron, reactive oxygen species, and NO in tissue homogenate, nuclear debris, and postmitochondrial fractions were mostly constant, but in mitochondria they continuously increased. An abrupt decrease in membrane potential and NAD(P)H at 12 h was also found in mitochondria. The respiratory control ratio was reduced slowly with a slight recovery at 72 h, suggesting uncoupling by iron.While the ATP content of tissue homogenate decreased steadily until 72 h, it showed a prominent increase in mitochondria at 12 h. Total iron and calcium concentration also progressively increased in mitochondria over 72 h. Enzyme activity of the oxidative phosphorylation system was significantly altered by iron injection: activities of complexes I, III, and IV were reduced considerably, but complex II activity and the ATPase activity of complex V were enhanced. A reversal of activity in complexes I and II at 12 h suggested reverse electron transfer due to iron overload. These results support the argument that mitochondrial activities including oxidative phosphorylation are modulated by excessive iron.

• The Korean Journal of Zoology
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• v.31 no.1
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• pp.62-70
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• 1988

The distribution of respiratory chain complexes in beef heart and human muscle mitochondria has been explored by immunoeledron microscopy with antibodies made against beef heart mltochondriai proteins in conjundion with protein A cofloidai gold (l2nm particles). The antibodies used were made against NADH-conezyme Q reductase(complex I), ubiquinol-cytochrome-c-oxldoreductase (complex III) and cytochrome-c-oxidase(complex IV). Labeling of bed heart tissue with any of these antihodies gave gold particles randomly distributed along the mitochondrial inner membrane. The labeling of muscle tIssue mitochondria from a patient with a mitochondrial myopathy localized by biochemical analysis to complex III was quantitated and compared with the labeling of human control muscle tissue mitochondria. Four kinds of morphological changes in the mitochondrial fine strudure in the myopathy patient tissue have been found; paracrystalline inclusions consistIng of densely packed multi- lamellar structures, globular crystalline inclusions with high electron density, multilamellar strudure inclusion body(compadly and irregularly arranged concentric whirl shaped cristae)and golbular cyrstalilne inclusions located in the center of the whirl shaped cristae. Compex I and cytochrome-c-oxldase antihodies reacted to the same level in the mitochondria containing the crystalline inclusions and control mitochondria. Antibodies to complex III reacted very poorly to the mitochondria containing the crystalline Inclusions but strongly to control mitchondria. The globular crystalline inclusions in the mitochondria are not reacted antibodies to respiratory chain complexes.

• BMB Reports
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• v.43 no.9
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• pp.614-621
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• 2010

Propamidine, an aromatic diamidine compound, is widely used as an antimicrobial agent. To uncover its mechanism on pathogenetic fungi, Botrytis cinerea as an object was used to investigate effects of propamidine in this paper. The transmission electron microscope results showed that the mitochondrial membranes were collapsed after propamidine treatment, followed that mitochondria were disrupted. Inhibition of whole-cell and mitochondrial respiration by propamidine suggested that Propamidine is most likely an inhibitor of electron transport within Botrytis cinerea mitochondria. Furthermore, the mitochondrial complex III activity were inhibited by propamidine.

• Applied Microscopy
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• v.17 no.1
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• pp.29-46
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• 1987

To study hexavalent chromium effects on mitochondrial electron transport, the activities of electron transport enzymes and conformational change of mitochondria treated with $40{\mu}M$ of sodium dichromate ($Na_{2}Cr_{2}O_{7}\;2H_{2}O$) were investigated. And so were those of liver mitochondria isolated from mouse intraperitoneally injected with sodium dichromate, 40mg per kg body weight. On both treatment with chromium(VI), the activities of electron transfer enzymes (Complex I and IV) were increased to some extent and the ultrastructural transformation of mitochondria from a condensed to an orthodox conformation was inhibited under State IV respiration. These results represent' inhibitory effect of hexavalent chromium on electron transport without inhibiting electron transfer enzymes (Complex I and IV) in mitochondria. On intraperitoneal treatment with hexavalent chromium as sodium dichromate and trivalent chromium as chromic chloride, containing 37.5 mg of chromium per kg body weight, respectively, the activities of electron transfer enzymes of liver isolated from mouse with chromium(VI) was reduced, but that with chromium(III) was not affected. And with chromium(VI), all mice after 12 hours of treatment died, only after 6 hours survived. With chromium(III), however, all survived. This indicates that hexavalent chromium is more toxic than trivalent chromiumin mouse liver.

• Animal cells and systems
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• v.7 no.1
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• pp.1-9
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• 2003

Programmed cell death, or apoptosis, is one of the most studied areas of modern biology. Apoptosis is a genetically regulated process, which plays an essential role in the development and homeostasis of higher organisms. Mitochondria, known to play a central role in regulating cellular metabolism, was found to be critical for regulating apoptosis induced under both physiological and pathological conditions. Mitochondria are a major source of reactive oxygen species (ROS) but they can also serve as its target during the apoptosis process. Release of apoptogenic factors from mitochondria, the best known of which is cytochrome c, leads to assembly of a large apoptosis-inducing complex called the apoptosome. Cysteine pretenses (called caspases) are recruited to this complex and, following their activation by proteolytic cleavage, activate other caspases, which in turn target for specific cleavage a large number of cellular proteins. The redox regulation of apoptosis during and after cytochrome c release is an area of intense investigation. This review summarizes what is known about the biological role of ROS and its targets in apoptosis with an emphasis on its intricate connections to mitochondria and the basic components of cell death.

• BMB Reports
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• v.51 no.6
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• pp.274-279
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• 2018

Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response ($UPR^{mt}$), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C. elegans against pathogens. Biological processes of C. elegans are usually conserved across phyla. Thus, understanding the mechanisms of mitochondria-mediated defense responses in C. elegans may provide insights into similar mechanisms in complex organisms, including mammals.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.6
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• pp.857-866
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• 2011

This study examined the metabolism of free radicals in hepatic mitochondria of goats induced by lipopolysaccharide (LPS), and investigated the effects of melatonin (MT). Forty-eight healthy goats ($10{\pm}1.2\;kg$) were randomly selected and divided into four groups: saline control, LPS, MT+LPS and MT. The goats within each group were3 sacrificed either 3 or 6 h after treatment and the livers removed to isolate mitochondria. The respiration control ratio (RCR), the ADP:O ratio, the oxidative phosphorylation ratio (OPR), the concentration of $H_2O_2$ and the activities of Complex I-IV were determined. The mitochondrial membrane potential ($\Delta\psi_m$) was analyzed by flow cytometry. The results showed that RCR, O/P and OPR of the LPS group decreased (p<0.05), as well as activities of respiratory complexes, whereas the generation of $H_2O_2$ in Complex III increased (p<0.05) after 3 h, while Complex II and III increased after 6 h. Also, it was found that the mitochondrial membrane potential of the LPS group declined (p<0.05). However, pre-treatment with MT attenuated the injury induced by LPS, which not only presented higher (p<0.05) RCR, O/P, OPR, and respiratory complex activities, but also maintained the $\Delta\psi_m$. Interestingly, it is revealed that, in the MT+LPS group, the generation of $H_2O_2$ increased firstly in 3 h, and then significantly (p<0.05).decreased after 6 h. In the MT group, the function of mitochondria, the transmenbrane potential and the generation of $H_2O_2$ were obviously improved compared to the control group. Conclusion: melatonin prevents damage caused by LPS on hepatic mitochondria of goats.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.113-121
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• 1987

Local anesthetics were investigated for their effects on mitochondrial electron transport system, production of superoxide radical from submitochondrial particles and malondialdehyde production through lipid per oxidation. Local anesthetics had various effects on activities of enzymes in electron transport chain. The activities of NADH dehydrogenase, NADH oxidase and NADH-ubiquinone oxidoreductase were effectively inhibited by lidocaine, procaine and dibucaine but slightly influenced by cocaine. The activities of succinate dehydrogenase, succinate-cytochrome c oxidoreductase and succinate-ubiquinone oxidoreductase were inhibited by lidocaine and dibucaine, but the succinate oxidase activity was stimulated by local anesthetics. Both dihydroubiquinone-cytochrome c oxidoreductase and cytochrome c oxidase activities were inhibited by local anesthetics. In these reactions, the response of Complex I segment to local anesthetics was greater than other Complex segments. Local anesthetics inhibited both the superoxide production from submitochondrial particles supplemented with succinate or NADH and the enhanced production of superoxide radicals by antimycin. The malondialdehyde production by oxygen free radicals was inhibited by local anesthetics. These results suggest that the inhibition of superoxide and malondialdehyde production caused by local anesthetics may be brought by suppression of the electron transport in mitochondria at sites in or near complex I segment.