• Integrative Medicine Research
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• v.2 no.4
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• pp.131-138
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• 2013

The skeletal muscle in our body is a major site for bioenergetics and metabolism during exercise. Carbohydrates and fats are the primary nutrients that provide the necessary energy required to maintain cellular activities during exercise. The metabolic responses to exercise in glucose and lipid regulation depend on the intensity and duration of exercise. Because of the increasing prevalence of obesity, recent studies have focused on the cellular and molecular mechanisms of obesity-induced insulin resistance in skeletal muscle. Accumulation of intramyocellular lipid may lead to insulin resistance in skeletal muscle. In addition, lipid intermediates (e.g., fatty acyl-coenzyme A, diacylglycerol, and ceramide) impair insulin signaling in skeletal muscle. Recently, emerging evidence linking obesity-induced insulin resistance to excessive lipid oxidation, mitochondrial overload, and mitochondrial oxidative stress have been provided with mitochondrial function. This review will provide a brief comprehensive summary on exercise and skeletal muscle metabolism, and discuss the potential mechanisms of obesity-induced insulin resistance in skeletal muscle.

• Journal of Microbiology and Biotechnology
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• v.6 no.4
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• pp.232-237
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• 1996

Growth yield of Desulfovibrio desulfuricans M6 was measured using different substrates. The cell yield of fermentative growth on pyruvate was 6.22 g cell $mol^{-l}$ pyruvate. Since 1 ATP is available from substrate-level phosphorylation from the oxidation of pyruvate to acetate, $Y_{ATP}$ of the bacterium should be the same as $Y_{pyruvate}$ (6.22 g cell $mol^{-l}$ ATP). The cell yields of the bacterium on different electron donors were measured with sulfate as the electron acceptor. Cell yields on lactate, pyruvate and $H_2$ were 9.39, 13.76 and 8.45 g cell $mol^{-l}$ substrate, respectively. From these figures ATP available from electron-transport phosphorylation (ETP) of the electron donors used was calculated. ATP produced by ETP of each electron donnor were 1.71 from pyruvate, 1.51 from lactate and 1.76 from $H_2$. These values show that electrons from the oxidation of lactate to pyruvate are consumed to reduce sulfate through a reverse electron transport mechanism requiring 0.2 ATP for each pair of electrons. Based on these results, discussions are made on the electron transport mechanism in the bacterium.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.71-77
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• 2012

Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal ${\beta}$-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.

• BMB Reports
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• v.48 no.11
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• pp.597-598
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• 2015

Mitochondrial respiratory defect is a key bioenergetics feature of hepatocellular carcinoma (HCC) cells. However, their involvement and roles in HCC development and progression remain unclear. Recently, we identified 10 common mitochondrial defect (CMD) signature genes that may be induced by retrograde signaling-mediated transcriptional reprogramming in response to HCC mitochondrial defects. HCC patients with enriched expression of these genes had poor prognostic outcomes, such as shorter periods of overall survival and recurrence-free survival. Nuclear protein 1 (NUPR1), a key transcription regulator, was up-regulated by Ca⁺⁺-mediated retrograde signaling. NUPR1-centric network analysis and a biochemical promoter-binding assay demonstrated that granulin (GRN) is a key downstream effector of NUPR1 for the regulation of HCC cell invasiveness; association analysis of the NUPR1-GRN pathway supported this conclusion. Mitochondrial respiratory defects and retrograde signaling thus play pivotal roles in HCC progression, highlighting the potential of the NUPR1-GRN axis as a novel diagnostic marker and therapeutic target for HCC.

• BMB Reports
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• v.46 no.8
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• pp.391-397
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• 2013

The ATP-inhibited Plant Mitochondrial $K^+$ Channel ($PmitoK_{ATP}$) was discovered about fifteen years ago in Durum Wheat Mitochondria (DWM). $PmitoK_{ATP}$ catalyses the electrophoretic $K^+$ uniport through the inner mitochondrial membrane; moreover, the co-operation between $PmitoK_{ATP}$ and $K^+/H^+$ antiporter allows such a great operation of a $K^+$ cycle to collapse mitochondrial membrane potential (${\Delta}{\Psi}$) and ${\Delta}pH$, thus impairing protonmotive force (${\Delta}p$). A possible physiological role of such ${\Delta}{\Psi}$ control is the restriction of harmful reactive oxygen species (ROS) production under environmental/oxidative stress conditions. Interestingly, DWM lacking ${\Delta}p$ were found to be nevertheless fully coupled and able to regularly accomplish ATP synthesis; this unexpected behaviour makes necessary to recast in some way the classical chemiosmotic model. In the whole, $PmitoK_{ATP}$ may oppose to large scale ROS production by lowering ${\Delta}{\Psi}$ under environmental/oxidative stress, but, when stress is moderate, this occurs without impairing ATP synthesis in a crucial moment for cell and mitochondrial bioenergetics.

• BMB Reports
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• v.53 no.1
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• pp.47-55
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• 2020

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease and has become a major socioeconomic issue in many developed countries. Currently available therapeutic agents for AD provide only symptomatic treatments, mainly because the complete mechanism of the AD pathogenesis is still unclear. Although several different hypotheses have been proposed, mitochondrial dysfunction has gathered interest because of its profound effect on brain bioenergetics and neuronal survival in the pathophysiology of AD. Various therapeutic agents targeting the mitochondrial pathways associated with AD have been developed over the past decade. Although most of these agents are still early in the clinical development process, they are used to restore mitochondrial function, which provides an alternative therapeutic strategy that is likely to slow the progression of the disease. In this mini review, we will survey the AD-related mitochondrial pathways and their small-molecule modulators that have therapeutic potential. We will focus on recently reported examples, and also overview the current challenges and future perspectives of ongoing research.

• BMB Reports
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• v.52 no.1
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• pp.13-23
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• 2019

Aging is accompanied by a time-dependent progressive deterioration of multiple factors of the cellular system. The past several decades have witnessed major leaps in our understanding of the biological mechanisms of aging using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial function, have emerged as prominent regulators of aging. Mitochondria have been considered to play a key role largely due to their production of reactive oxygen species (ROS), resulting in DNA damage that accumulates over time and ultimately causes cellular failure. This theory, known as the mitochondrial free radical theory of aging (MFRTA), was favored by the aging field, but increasing inconsistent evidence has led to criticism and rejection of this idea. However, MFRTA should not be hastily rejected in its entirety because we now understand that ROS is not simply an undesired toxic metabolic byproduct, but also an important signaling molecule that is vital to cellular fitness. Notably, mitochondrial function, a term traditionally referred to bioenergetics and apoptosis, has since expanded considerably. It encompasses numerous other key biological processes, including the following: (i) complex metabolic processes, (ii) intracellular and endocrine signaling/communication, and (iii) immunity/inflammation. Here, we will discuss shortcomings of previous concepts regarding mitochondria in aging and their emerging roles based on recent advances. We will also discuss how the mitochondrial genome integrates with major theories on the evolution of aging.

• ALGAE
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• v.37 no.4
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• pp.301-316
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• 2022

The red alga Compsopogon caeruleus can generally be found in tropical and subtropical waters worldwide. In addition to its natural habitats, this species may be found in waters that receive abnormally hot water, e.g., from powerhouses. To date, the presence of C. caeruleus has not been observed in thermally polluted lacustrine ecosystems in Poland, which has a moderate climate. The thalli of this red alga were found growing on Vallisneria spiralis in Lichenskie Lake. Importantly, this paper presents a previously unknown relationship between the temperature (20, 25, 30, 35, and 40℃) and oxygen requirements of C. caeruleus (based on ex situ measurements of O₂ consumption by thalli). Surprisingly, 35℃ can be the optimum temperature for C. caeruleus, and this temperature is higher than the values reported by some previous thermal analyses by approximately 10℃. Additionally, we reviewed and mapped the distribution of this nonnative and mesophilic red alga in natural / seminatural water ecosystems in Europe. Finally, we propose that the occurrence of C. caeruleus mature thalli can be a novel, simple and easy-to-recognize bioindicator of artificially and permanently heated waters in moderate climate zones by a regular discharge of postindustrial water.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.567-577
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• 2017

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in $O_2$ respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.5.1-5.15
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• 2018

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.