• The Korean Journal of Physiology and Pharmacology
• /
• v.11 no.2
• /
• pp.57-64
• /
• 2007

Ischemic preconditioning (IPC) is known to protect the heart against ischemia/reperfusion (IR)-induced injuries, and regional differences in the mitochondrial antioxidant state during IR or IPC may promote the death or survival of viable and infarcted cardiac tissues under oxidative stress. To date, however, the interplay between the mitochondrial antioxidant enzyme system and the level of reactive oxygen species (ROS) in the body has not yet been resolved. In the present study, we examined the effects of IR- and IPC-induced oxidative stresses on mitochondrial function in viable and infarcted cardiac tissues. Our results showed that the mitochondria from viable areas in the IR-induced group were swollen and fused, whereas those in the infarcted area were heavily damaged. IPC protected the mitochondria, thus reducing cardiac injury. We also found that the activity of the mitochondrial antioxidant enzyme system, which includes manganese superoxide dismutase (Mn-SOD), was enhanced in the viable areas compared to the infarcted areas in proportion with decreasing levels of ROS and mitochondrial DNA (mtDNA) damage. These changes were also present between the IPC and IR groups. Regional differences in Mn-SOD expression were shown to be related to a reduction in mtDNA damage as well as to the release of mitochondrial cytochrome c (Cyt c). To the best of our knowledge, this might be the first study to explore the regional mitochondrial changes during IPC. The present findings are expected to help elucidate the molecular mechanism involved in IPC and helpful in the development of new clinical strategies against ischemic heart disease.

• Archives of Pharmacal Research
• /
• v.7 no.1
• /
• pp.63-64
• /
• 1984

This major sites of liquidperoxidation-damage within the cell are at biomembrances, especially those of subcellular organells such as mitochondria and microsomes whose membranes contain relatively large amount of polyunsaturated fatty acids. Mitochondria are the power plants of eukaryotic cells. Hence their damage by liquid peroxidation can profoundly affect cellular function.

• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.1
• /
• pp.15-24
• /
• 2022

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H₃R₉ exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H₃R₉ showed a better rescue action compared to that of MTS-H₃R₉. GA-MTS-H₃R₉ dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H₃R₉ towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTS-H₃R₉ alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H₃R₉ showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H₃R₉. We showed that GA-MTS-H₃R₉ can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

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

• Molecules and Cells
• /
• v.41 no.1
• /
• pp.18-26
• /
• 2018

Mitochondrial quality control systems are essential for the maintenance of functional mitochondria. At the organelle level, they include mitochondrial biogenesis, fusion and fission, to compensate for mitochondrial function, and mitophagy, for degrading damaged mitochondria. Specifically, in mitophagy, the target mitochondria are recognized by the autophagosomes and delivered to the lysosome for degradation. In this review, we describe the mechanisms of mitophagy and the factors that play an important role in this process. In particular, we focus on the roles of mitophagy adapters and receptors in the recognition of damaged mitochondria by autophagosomes. In addition, we also address a functional association of mitophagy with mitochondrial dynamics through the interaction of mitophagy adaptor and receptor proteins with mitochondrial fusion and fission proteins.

• BMB Reports
• /
• v.45 no.1
• /
• pp.1-6
• /
• 2012

Hsp90 is one of the most conserved molecular chaperones ubiquitously expressed in normal cells and over-expressed in cancer cells. A pool of Hsp90 was found in cancer mitochondria and the expression of the mitochondrial Hsp90 homolog, TRAP1, was also elevated in many cancers. The mitochondrial pool of chaperones plays important roles in regulating mitochondrial integrity, protecting against oxidative stress, and inhibiting cell death. Pharmacological inactivation of the chaperones induced mitochondrial dysfunction and concomitant cell death selectively in cancer cells, suggesting they can be target proteins for the development of cancer therapeutics. Several drug candidates targeting TRAP1 and Hsp90 in the mitochondria have been developed and have shown strong cytotoxic activity in many cancers, but not in normal cells in vitro and in vivo. In this review, recent developments in the study of mitochondrial chaperones and the mitochondria-targeted chaperone inhibitors are discussed.

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

• BMB Reports
• /
• v.29 no.4
• /
• pp.343-352
• /
• 1996

The biosynthesis of phospholipid and the composition of fatty acid were analyzed in mitochondria isolated from Chlorella ellipsoidea treated with carbon sources (glucose, sucrose, raffinose) during the culture. The growth of Chlorella and total lipid contents in mitochondria treated with various carbon sources was increased to compare with the control. When Chlorella mitochondria was treated with various carbon sources, four kinds of phospholipid were increased predominantly. The major fatty acids utilized for the biosynthesis of the phospholipid were analyzed linoleic acid (average 25.18%) and stearic acid (average 10.52%) in the control. But, it was shown that the major fatty acids in Chlorella mitochondria treated with glucose were stearic acid (average 30.93%), palmitic acid (average 17.47%) and stearic acid (average 20.31%), linoleic acid (average 16.68%) in sucrose treatment and oleic acid (average 17.17%), palmitic acid (average 15.64%) in raffinose treatment.

• Development and Reproduction
• /
• v.3 no.1
• /
• pp.15-19
• /
• 1999

Preeclampsia is a common, pregnancy-induced hypertensive disease leading to severe morbidity in the mother and fetus. Although the etiology of preeclampsia remains unclear, many studies focus mutation of placental mitochondria as the cause of this disease. This review covers mutation of placental mitochondria as the possible etiology of preeclampsia, prevention and treatment strategies based on the hypothesis of mutation of placental mitochondria in the etiology of preeclampsia.

• Applied Microscopy
• /
• v.43 no.3
• /
• pp.117-121
• /
• 2013

Mitochondrion is an important intracellular organelle controlling energy production essential for cell survival. In addition, it is closely related to cellular apoptosis and necrosis. Linear, branched, circular, and ball-shaped mitochondria have been reported. Recent research suggests that mitochondrial morphology may reflect functional status of the cell. In this study, we investigated the density and ratio of the each morphological categories of mitochondria in a few normal cultured cells; astrocyte, HeLa and COS7 cells, of which metabolic activities are different, with high voltage electron microscopy. The absolute number and relative number per unit area of mitochondria was largest in astrocyte. But, the proportion of different mitochondrial shape was similar among cells. These results shows the numerical profiles but not morphological profiles of mitochondria are related to the metabolic activity of each cell line.