• BMB Reports
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• v.52 no.1
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• pp.5-12
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• 2019

Organismal aging is accompanied by a host of progressive metabolic alterations and an accumulation of senescent cells, along with functional decline and the appearance of multiple diseases. This implies that the metabolic features of cell senescence may contribute to the organism's metabolic changes and be closely linked to age-associated diseases, especially metabolic syndromes. However, there is no clear understanding of senescent metabolic characteristics. Here, we review key metabolic features and regulators of cellular senescence, focusing on mitochondrial dysfunction and anabolic deregulation, and their link to other senescence phenotypes and aging. We further discuss the mechanistic involvement of the metabolic regulators mTOR, AMPK, and GSK3, proposing them as key metabolic switches for modulating senescence.

• Journal of Microbiology and Biotechnology
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• v.6 no.6
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• pp.425-431
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• 1996

The enzymatic characteristics of Alcaligenes latus were investigated by measuring the variations of various enzyme activities related to biosynthesis and degradation of poly-${\beta}$-hydroxybutyrate (PHB) during cultivation. All PHB biosynthetic enzymes, ${\beta}$-ketothiolase, acetoacetyl-CoA reductase, and PHB synthase, were activated gradually at the PHB accumulation stage, and the PHB synthase showed the highest value among three enzymes. This indicates that the rate of PHB biosynthesis is mainly controlled by either ${\beta}$-ketothiolase or acetoacetyl-CoA reductase rather than PHB synthase. The enzymatic activities related to the degradation of PHB were also measured, and the degradation of PHB was controlled by the activity of PHB depolymerase. The effect of supplements of metabolic regulators, citrate and tyrosine, was also investigated, and the activity of glucose-6-phosphate dehydrogenase was increased by metabolic regulators, especially by tyrosine. The activities of ${\beta}$-ketothiolase and acetoacetyl-CoA reductase were also activated by citrate and tyrosine, while the activity of PHB depolymerase was depressed. The increased rate and yield of PHB biosynthesis by metabolic regulators may be due to the increment of acetyl-CoA concentration either by the repression of the TCA cycle by citrate through product inhibition or by the activation of sucrose metabolism by the supplemented tyrosine.

• 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.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.273-278
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• 2018

Bile acids are major constituents of bile and known to help absorb dietary fat and fat-soluble vitamins in the gastrointestinal tract. In the past few decades, many studies have shown that bile acids not only play a role in fat digestion but also function as broad range of signal transduction hormones by binding to various receptors present in cell membranes or nuclei. Bile acid receptors are distributed in a wide range of organs and tissues in the human body. They perform multitudes of physiological functions with complex mechanisms. When bile acids bind to their receptors, they regulate fat and glucose metabolism in a tissue-specific way. In addition, bile acids are shown to inhibit inflammation and fibrosis in the liver. Considering the roles of bile acids as metabolic regulators, bile acids and their receptors can be very attractive targets in treating metabolic disorders. In the future, if roles of bile acids and their receptors are further clarified, they will be the novel target of drugs in the treatment of various metabolic diseases.

• Journal of Applied Biological Chemistry
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• v.56 no.1
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• pp.37-42
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• 2013

In eukaryotes, most of the genome are transcribed, however only a small proportion of total transcripts encodes for protein, thus resulting in many of noncoding RNAs. In order to recover DNA damage including DNA double-strand breaks (DSBs) eukaryotes have evolved complex mechanisms and these are processed through coordinated mechanisms of protein sensors, transducers, and effectors including RNAs. During recent years, small RNAs have been increasingly studied and gradually considered as key regulators in various aspects of biology. Upon DNA damage, small RNAs including diRNAs (DSB induced RNA) are generated in both plant and human cell lines. Inhibition of their biogenesis has severe influence on DSB repair system.

• Molecules and Cells
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• v.46 no.12
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• pp.727-735
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• 2023

Stem cells require high amounts of energy to replicate their genome and organelles and differentiate into numerous cell types. Therefore, metabolic stress has a major impact on stem cell fate determination, including self-renewal, quiescence, and differentiation. Lysosomes are catabolic organelles that influence stem cell function and fate by regulating the degradation of intracellular components and maintaining cellular homeostasis in response to metabolic stress. Lysosomal functions altered by metabolic stress are tightly regulated by the transcription factor EB (TFEB) and TFE3, critical regulators of lysosomal gene expression. Therefore, understanding the regulatory mechanism of TFEB-mediated lysosomal function may provide some insight into stem cell fate determination under metabolic stress. In this review, we summarize the molecular mechanism of TFEB/TFE3 in modulating stem cell lysosomal function and then elucidate the role of TFEB/TFE3-mediated transcriptional activity in the determination of stem cell fate under metabolic stress.

• KSBB Journal
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• v.10 no.2
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• pp.143-148
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• 1995

The effects of various elicitors, metabolic inhibitors and growth regulators on the production of diterpenoid anticancer agent taxol were investigated in cell suspension cultures of Taxus brevifolia. Cell cultures of T. brevifolia were treated by 5 kinds of biotic elicitors, 5 kinds of abiotic elicitors, 2 kinds of metabolic inhibitors and 8 kinds of growth regulators at the end of exponential growth phase. Among those treatments, chlorocholine chloride-an inhibitor of plant steroid metabolism-increased the taxol production most significantly. From a series of optimization studies, it was found that the addition of 1mM of chlorocholine chloride at the 9th day of culture was the best for taxol production. Taxol yield under this condition was 0.72mg/$\ell$.

• Molecules and Cells
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• v.38 no.9
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• pp.750-758
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• 2015

Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2005.11a
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• pp.65-70
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• 2005

A growing body of evidence shows that nitric oxide $({\cdot}NO)$ and ${\cdot}NO-derived$ reactive nitrogen species (RNS) act as both plant physiological regulators and stressors. However, very little is known concerning metabolism of RNS in plant cells. In this paper, we explore a plant metabolic basis for RNS, with special emphasis on the possible relationship to nitrogen assimilation, and discuss the potential of the metabolic engineering for plant-biotechnological application.

• IMMUNE NETWORK
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• v.16 no.2
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• pp.85-98
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• 2016

The mitogen-activated protein kinases (MAPKs) are key regulators of cell growth and survival in physiological and pathological processes. Aberrant MAPK signaling plays a critical role in the development and progression of human cancer, as well as in determining responses to cancer treatment. The MAPK phosphatases (MKPs), also known as dual-specificity phosphatases (DUSPs), are a family of proteins that function as major negative regulators of MAPK activities in mammalian cells. Studies using mice deficient in specific MKPs including MKP1/DUSP1, PAC-1/DUSP2, MKP2/DUSP4, MKP5/DUSP10 and MKP7/DUSP16 demonstrated that these molecules are important not only for both innate and adaptive immune responses, but also for metabolic homeostasis. In addition, the consequences of the gain or loss of function of the MKPs in normal and malignant tissues have highlighted the importance of these phosphatases in the pathogenesis of cancers. The involvement of the MKPs in resistance to cancer therapy has also gained prominence, making the MKPs a potential target for anti-cancer therapy. This review will summarize the current knowledge of the MKPs in cancer development, progression and treatment outcomes.