• Mycobiology
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• v.42 no.4
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• pp.427-431
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• 2014

Mitochondrial protein Nfu1 plays an important role in the assembly of mitochondrial Fe-S clusters and intracellular iron homeostasis in the model yeast Saccharomyces cerevisiae. In this study, we identified the Nfu1 ortholog in the human fungal pathogen Cryptococcus neoformans. Our data showed that C. neoformans Nfu1 localized in the mitochondria and influenced homeostasis of essential metals such as iron, copper and manganese. Marked growth defects were observed in the mutant lacking NFU1, which suggests a critical role of Nfu1 in Fe-S cluster biosynthesis and intracellular metal homeostasis in C. neoformans.

• Animal cells and systems
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• v.16 no.4
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• pp.269-273
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• 2012

Controlling metabolism throughout life is a necessity for living creatures, and perturbation of energy balance elicits disorders such as type-2 diabetes mellitus and cardiovascular disease. $Ca^{2+}$ plays a key role in regulating energy generation. $Ca^{2+}$ homeostasis of the endoplasmic reticulum (ER) lumen is maintained through the action of $Ca^{2+}$ channels and the $Ca^{2+}$ ATPase pump. Once released from the ER, $Ca^{2+}$ is taken up by mitochondria where it facilitates energy metabolism. Mitochondrial $Ca^{2+}$ serves as a key metabolic regulator and determinant of cell fate, necrosis, and/or apoptosis. Here, we focus on $Ca^{2+}$ transport from the ER to mitochondria, and $Ca^{2+}$-dependent regulation of mitochondrial energy metabolism.

• 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.41 no.1
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• pp.11-22
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• 2008

Apoptosis (programmed cell death) is a cellular self-destruction mechanism that is essential for a variety of biological events, such as developmental sculpturing, tissue homeostasis, and the removal of unwanted cells. Mitochondria play a crucial role in regulating cell death. $Ca^{2+}$ has long been recognized as a participant in apoptotic pathways. Mitochondria are known to modulate and synchronize $Ca^{2+}$ signaling. Massive accumulation of $Ca^{2+}$ in the mitochondria leads to apoptosis. The $Ca^{2+}$ dynamics of ER and mitochondria appear to be modulated by the Bcl-2 family proteins, key factors involved in apoptosis. The number and morphology of mitochondria are precisely controlled through mitochondrial fusion and fission process by numerous mitochondria-shaping proteins. Mitochondrial fission accompanies apoptotic cell death and appears to be important for progression of the apoptotic pathway. Here, we highlight and discuss the role of mitochondrial calcium handling and mitochondrial fusion and fission machinery in apoptosis.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.85-90
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• 2017

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

• BMB Reports
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• v.50 no.4
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• pp.164-174
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• 2017

Mitochondria are cytosolic organelles essential for generating energy and maintaining cell homeostasis. Despite their critical function, the handful of proteins expressed by the mitochondrial genome is insufficient to maintain mitochondrial structure or activity. Accordingly, mitochondrial metabolism is fully dependent on factors encoded by the nuclear DNA, including many proteins synthesized in the cytosol and imported into mitochondria via established mechanisms. However, there is growing evidence that mammalian mitochondria can also import cytosolic noncoding RNA via poorly understood processes. Here, we summarize our knowledge of mitochondrial RNA, discuss recent progress in understanding the molecular mechanisms and functional impact of RNA import into mitochondria, and identify rising challenges and opportunities in this rapidly evolving field.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.1
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• pp.1-11
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• 2023

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine.

• Toxicological Research
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• v.30 no.4
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• pp.243-250
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• 2014

Mitochondrial integrity is critical for maintaining proper cellular functions. A key aspect of regulating mitochondrial homeostasis is removing damaged mitochondria through autophagy, a process called mitophagy. Autophagy dysfunction in various disease states can inactivate mitophagy and cause cell death, and defects in mitophagy are becoming increasingly recognized in a wide range of diseases from liver injuries to neurodegenerative diseases. Here we highlight our current knowledge on the mechanisms of mitophagy, and discuss how alterations in mitophagy contribute to disease pathogenesis. We also discuss mitochondrial dynamics and potential interactions between mitochondrial fusion, fission and mitophagy.

• Molecules and Cells
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• v.43 no.1
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• pp.10-22
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• 2020

Mitochondria have several quality control mechanisms by which they maintain cellular homeostasis and ensure that the molecular machinery is protected from stress. Mitophagy, selective autophagy of mitochondria, promotes mitochondrial quality control by inducing clearance of damaged mitochondria via the autophagic machinery. Accumulating evidence suggests that mitophagy is modulated by various microbial components in an attempt to affect the innate immune response to infection. In addition, mitophagy plays a key role in the regulation of inflammatory signaling, and mitochondrial danger signals such as mitochondrial DNA translocated into the cytosol can lead to exaggerated inflammatory responses. In this review, we present current knowledge on the functional aspects of mitophagy and its crosstalk with innate immune signaling during infection. A deeper understanding of the role of mitophagy could facilitate the development of more effective therapeutic strategies against various infections.

• Journal of Chest Surgery
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• v.19 no.2
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• pp.197-208
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• 1986

Propranolol is one of clinically useful antiarrhythmic agents and electrophysiologically classified as group II. And the negative inotropic effect which is not related to adrenolytic effect has been demonstrated with high concentration of propranolol. On the other hand, it has been well known that the calcium plays a central role in excitation-contraction coupling process of myocardium and also in electrophysiological changes of cell membrane. Author studies the effect of propranolol on calcium uptake and release in sarcoplasmic reticulum and mitochondria prepared from porcine myocardium to investigate the mechanism of action of propranolol on myocardium. The results are summarized as follow: 1] The maximum Ca++-uptake of sarcoplasmic reticulum is inhibited by propranolol in a dose dependent manner. 2] The release of calcium from sarcoplasmic reticulum is not affected by propranolol but with higher than 1x10-3 M of propranolol, rate of calcium release from sarcoplasmic reticulum is decreased. 3] Propranolol inhibits the maximum uptake and uptake rate of calcium in mitochondria non-competitively. [Ki = 6.21 x 10-4 M] 4] The rate of Na+ induced calcium release from mitochondrion shows a function of [Na+]2 and is inhibited by propranolol with the concentration significantly lower than that affect the calcium uptake in sarcoplasmic reticulum and in mitochondria [Ki = 2.91 x 10-5 M]. These results suggest that propranolol affects the intracellular calcium homeostasis which may considered to be one of the mechanism of action of propranolol on myocardium.