• Molecules and Cells
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• v.45 no.4
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• pp.193-201
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• 2022

Excessive production of reactive oxygen species (ROS) is a key phenomenon in tumor necrosis factor (TNF)-α-induced cell death. However, the role of ROS in necroptosis remains mostly elusive. In this study, we show that TNF-α induces the mitochondrial accumulation of superoxide anions, not H₂O₂, in cancer cells undergoing necroptosis. TNF-α-induced mitochondrial superoxide anions production is strictly RIP3 expression-dependent. Unexpectedly, TNF-α stimulates NADPH oxidase (NOX), not mitochondrial energy metabolism, to activate superoxide production in the RIP3-positive cancer cells. In parallel, mitochondrial superoxide-metabolizing enzymes, such as manganese-superoxide dismutase (SOD2) and peroxiredoxin III, are not involved in the superoxide accumulation. Mitochondrial-targeted superoxide scavengers and a NOX inhibitor eliminate the accumulated superoxide without affecting TNF-α-induced necroptosis. Therefore, our study provides the first evidence that mitochondrial superoxide accumulation is a consequence of necroptosis.

• BMB Reports
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• v.52 no.12
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• pp.679-688
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• 2019

The decrease of metabolism in the brain has been observed as the important lesions of Alzheimer's disease (AD) from the early stages of diagnosis. The cumulative evidence has reported that the failure of mitochondria, an organelle involved in diverse biological processes as well as energy production, maybe the cause or effect of the pathogenesis of AD. Both amyloid and tau pathologies have an impact upon mitochondria through physical interaction or indirect signaling pathways, resulting in the disruption of mitochondrial function and dynamics which can trigger AD. In addition, mitochondria are involved in different biological processes depending on the specific functions of each cell type in the brain. Thus, it is necessary to understand mitochondrial dysfunction as part of the pathological phenotypes of AD according to each cell type. In this review, we summarize that 1) the effects of AD pathology inducing mitochondrial dysfunction and 2) the contribution of mitochondrial dysfunction in each cell type to AD pathogenesis.

• Molecules and Cells
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• v.41 no.12
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• pp.1000-1007
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• 2018

Mitochondria and endoplasmic reticulum (ER) are essential organelles in eukaryotic cells, which play key roles in various biological pathways. Mitochondria are responsible for ATP production, maintenance of $Ca^{2+}$ homeostasis and regulation of apoptosis, while ER is involved in protein folding, lipid metabolism as well as $Ca^{2+}$ homeostasis. These organelles have their own functions, but they also communicate via mitochondrial-associated ER membrane (MAM) to provide another level of regulations in energy production, lipid process, $Ca^{2+}$ buffering, and apoptosis. Hence, defects in MAM alter cell survival and death. Here, we review components forming the molecular junctions of MAM and how MAM regulates cellular functions. Furthermore, we discuss the effects of impaired ER-mitochondrial communication in various neurodegenerative diseases.

• BMB Reports
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• v.51 no.11
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• pp.549-556
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• 2018

Mitochondria are ubiquitous and multi-functional organelles involved in diverse metabolic processes, namely energy production and biomolecule synthesis. The intracellular mitochondrial morphology and distribution change dynamically, which reflect the metabolic state of a given cell type. A dramatic change of the mitochondrial dynamics has been observed in early development that led to further investigations on the relationship between mitochondria and the process of development. A significant developmental process to focus on, in this review, is a differentiation of neural progenitor cells into neurons. Information on how mitochondria-regulated cellular energetics is linked to neuronal development will be discussed, followed by functions of mitochondria and associated diseases in neuronal development. Lastly, the potential use of mitochondrial features in analyzing various neurodevelopmental diseases will be addressed.

• Animal Bioscience
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• v.37 no.4
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• pp.631-639
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• 2024

Objective: This study evaluates goat sperm motility in response to metabolic substrates and various inhibitors, aiming to assess the relative contribution of glycolysis and mitochondrial oxidation for sperm movement and adenosine triphosphate (ATP) production. Methods: In the present study, two main metabolic substrates; 0 to 0.5 mM glucose and 0 to 30 mM pyruvate were used to evaluate their contribution to sperm movements of goats. Using a 3-chloro-1,2-propanediol (3-MCPD), a specific inhibitor for glycolysis, and carbonyl cyanide 3-chlorophenylhydrazone as an inhibitor for oxidative phosphorylation, cellular mechanisms into ATP-generating pathways in relation to sperm movements and ATP production were observed. Data were analysed using one-way analysis of variance for multiple comparisons. Results: Sperm motility analysis showed that either glucose or pyruvate supported sperm movement during 0 to 30 min incubation. However, the supporting effects were abolished by the addition of a glycolysis inhibitor or mitochondrial uncoupler, concomitant with a significant decrease in ATP production. Although oxidative phosphorylation produces larger ATP concentrations than those from glycolysis, sperm progressivity in relation to these two metabolic pathways is comparable. Conclusion: Based on the present study, we suggest that goat sperm use glucose and pyruvate to generate cellular energy through glycolysis and mitochondrial respiration pathways to maintain sperm movement.

• Journal of Yeungnam Medical Science
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• v.41 no.2
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• pp.61-73
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• 2024

Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.

• Journal of Microbiology and Biotechnology
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• v.18 no.4
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• pp.778-783
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• 2008

Anthrax is an infectious disease caused by toxigenic strains of the Gram-positive bacterium Bacillus anthracis. To identify the mitochondrial proteins that are expressed differently in murine macrophages infected with spores of B. anthracis Sterne, proteomic and MALDI-TOF/MS analyses of uninfected and infected macrophages were conducted. As a result, 13 mitochondrial proteins with different expression patterns were discovered in the infected murine macrophages, and some were identified as ATP5b, NIAP-5, ras-related GTP binding protein B isoform CRAa, along with several unnamed proteins. Among these proteins, ATP5b is related to energy production and cytoskeletal rearrangement, whereas NIAP-5 causes apoptosis of host cells due to binding with caspase-9. Therefore, this paper focused on ATP5b, which was found to be down regulated following infection. The downregulated ATP5b also reduced ATP production in the murine macrophages infected with B. anthracis spores. Consequently, this study represents the first mitochondrial proteome analysis of infected macrophages.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.759-770
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• 2022

Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD⁺-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.39-44
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• 2018

In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.

• Journal of Photoscience
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• v.1 no.1
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• pp.9-14
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• 1994

Exposure of isolated intact mitochondria to near UV to visible light resulted in not only loss of respiration, the most well-documented phenomenon regarding phototoxic effects in the respiring organelles, but also lipid peroxidation of membranes and mitochondrial swelling; these turned out to be O$_2$-dependent and thus prevented by anaerobiosis, enhanced by a partial deuteration of the suspension medium, and suppressed by the presence of a singlet oxygen ($^1O_2$) scavenger. Measurements of the spectral dependence of such detrimental effects of light on mitochondrial structure and function revealed that all the resulting spectra bear a significant resemblance to the action spectrum for photogeneration of $^1O_2$ from mitochondrial membranes, which in turn carries the spectral characteristics of light absorption by mitochondrial Fe-S centers. Futhermore, destructing the Fe-S centers by a mercurial treatment of mitochondria brought about a striking reduction of the light-induced membrane peroxidation and swelling of mitochondria. These results are consistent with the suggestion that the impairment of functional, structural integrity of mitochondria caused by strong irradiation is directly related to the production of $^1O_2$ in mitochondria, photosensitized by the Fe-S centers. This paper also presents kinetic data which indicate that, among various membrane-bound protein systems associated with mitochondrial energy metabolism, the respiratory chain is the primary target for photodamage.