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Nanoscale Jan 2020Selenium nanoparticles (SeNPs) can induce reactive oxygen species (ROS)-mediated cell death when accumulated in cancer cells, while rendering anti-oxidation and cancer...
Selenium nanoparticles (SeNPs) can induce reactive oxygen species (ROS)-mediated cell death when accumulated in cancer cells, while rendering anti-oxidation and cancer prevention in healthy tissues at low doses. Although they are promising anticancer agents with fewer side effects, their application is limited by their relative low toxicity to cancer cells. Therefore, we propose a mitochondrion-targeting strategy to improve their cancer cell killing efficiency. Such mitochondrion-targeted SeNPs could efficiently increase ROS production and mitochondrion damage in cancer cells; however, only a slightly increased toxicity to normal cells was observed, indicating a potentially better therapeutic window for anticancer treatments.
Topics: Antineoplastic Agents; HeLa Cells; Humans; Metal Nanoparticles; Mitochondria; Neoplasms; Reactive Oxygen Species; Selenium
PubMed: 31913383
DOI: 10.1039/c9nr09039h -
Genome Biology 2003Experimental analyses of the proteins found in the mitochondria of yeast, humans and Arabidopsis have confirmed some expectations but given some surprises and some... (Review)
Review
Experimental analyses of the proteins found in the mitochondria of yeast, humans and Arabidopsis have confirmed some expectations but given some surprises and some insights into the evolutionary origins of mitochondrial proteins.
Topics: Evolution, Molecular; Humans; Mitochondria; Mitochondrial Proteins
PubMed: 12801406
DOI: 10.1186/gb-2003-4-6-218 -
FEMS Microbiology Reviews Jul 2006The mitochondrion of Plasmodium species is a validated drug target. However, very little is known about the functions of this organelle. In this review, we utilize data... (Review)
Review
The mitochondrion of Plasmodium species is a validated drug target. However, very little is known about the functions of this organelle. In this review, we utilize data available from the Plasmodium falciparum genome sequencing project to piece together putative metabolic pathways that occur in the parasite, comparing this with the existing biochemical and cell biological knowledge. The Plasmodium mitochondrion contains both conserved and unusual features, including an active electron transport chain and many of the necessary enzymes for coenzyme Q and iron-sulphur cluster biosynthesis. It also plays an important role in pyrimidine metabolism. The mitochondrion participates in an unusual hybrid haem biosynthesis pathway, with enzymes localizing in both the mitochondrion and plastid organelles. The function of the tricarboxylic acid cycle in the mitochondrion is unclear. We discuss directions for future research into this fascinating, yet enigmatic, organelle.
Topics: Animals; Citric Acid Cycle; Electron Transport; Folic Acid; Heme; Humans; Iron-Sulfur Proteins; Mitochondria; Plasmodium falciparum; Ubiquinone
PubMed: 16774588
DOI: 10.1111/j.1574-6976.2006.00027.x -
Parasitology Nov 2004Mitochondria of the malaria parasite Plasmodium falciparum are morphologically different between the asexual and sexual blood stages (gametocytes). In this paper recent... (Review)
Review
Mitochondria of the malaria parasite Plasmodium falciparum are morphologically different between the asexual and sexual blood stages (gametocytes). In this paper recent findings of mitochondrial heterogeneity are reviewed based on their ultrastructural characteristics, metabolic activities and the differential expression of their genes in these 2 blood stages of the parasite. The existence of NADH dehydrogenase (complex I), succinate dehydrogenase (complex II), cytochrome c reductase (complex III) and cytochrome c oxidase (complex IV) suggests that the biochemically active electron transport system operates in this parasite. There is also an alternative electron transport branch pathway, including an anaerobic function of complex II. One of the functional roles of the mitochondrion in the parasite is the coordination of pyrimidine biosynthesis, the electron transport system and oxygen utilization via dihydroorotate dehydrogenase and coenzyme Q. Complete sets of genes encoding enzymes of the tricarboxylic acid cycle and the ATP synthase complex are predicted from P. falciparum genomics information. Other metabolic roles of this organelle include membrane potential maintenance, haem and coenzyme Q biosynthesis, and oxidative phosphorylation. Furthermore, the mitochondrion may be a chemotherapeutic target for antimalarial drug development. The antimalarial drug atovaquone targets the mitochondrion.
Topics: Animals; Electron Transport; Gene Expression Regulation, Enzymologic; Life Cycle Stages; Malaria, Falciparum; Mitochondria; Oxygen Consumption; Plasmodium falciparum
PubMed: 15552397
DOI: 10.1017/s0031182004005888 -
Theranostics 2022Tumor energy metabolism has been a well-appreciated target of cancer therapy; however, the metabolism change of cancer cells between oxidative phosphorylation and...
Tumor energy metabolism has been a well-appreciated target of cancer therapy; however, the metabolism change of cancer cells between oxidative phosphorylation and glycolysis poses a challenge to the above. In this study, we constructed an innovative mitochondrion-targeted supramolecular "nano-boat" based on peptide self-assembly for tumor combined chemo-radiotherapy by simultaneously inhibiting the dual energy metabolism. A lipophilic self-assembled peptide and a positively charged cyclen were integrated to fabricate a brand new mitochondrion-targeted nano-platform for the first time. The indices of mitochondrial dysfunction including mitochondrial membrane potential, apoptosis proteins expression and ultrastructure change were evaluated using a JC-1 probe, western blotting and biological transmission electron microscopy, respectively. Energy metabolism assays were conducted on a Seahorse XF24 system by detecting the oxygen consumption rate and the glycolytic proton efflux rate. The radio-sensitization effect was investigated by colony formation, the comet assay, and γ-H2AX staining. The supramolecular "nano-boat" could selectively kill cancer cells by much higher enrichment and reactive oxygen species generation than those in normal cells. In the cancer cells treated with the supramolecular "nano-boat", the dysfunctional morphological changes of the mitochondrial ultrastructure including swelling and pyknosis were evidently observed, and the endogenous mitochondrial apoptosis pathway was effectively triggered by abundant of cytochrome C leaking out. Concurrently, the dual metabolic pathways of glycolysis and oxidative phosphorylation were severely inhibited. More importantly, the supramolecular "nano-boat" displayed an excellent radio-sensitization effect with a sensitization enhancement ratio value as high as 2.58, and hence, efficiently combining radiotherapy yielded an enhanced chemo-radiotherapy effect. Our study demonstrated that the rationally designed peptide-based "nano-boat" could efficiently induce cancer cell apoptosis by the energy metabolism inhibition involving multiple pathways, which may provide the motivation for designing novel and universal mitochondria-targeted drug delivery systems for cancer therapy.
Topics: Cell Line, Tumor; Chemoradiotherapy; Energy Metabolism; Mitochondria; Oxidative Phosphorylation; Reactive Oxygen Species
PubMed: 35154487
DOI: 10.7150/thno.67543 -
Proceedings of the National Academy of... May 1970The morphological and biochemical properties of isolated mitochondrial inner and outer membranes are summarized and discussed in relation to the functional organization... (Review)
Review
The morphological and biochemical properties of isolated mitochondrial inner and outer membranes are summarized and discussed in relation to the functional organization of the intact mitochondrion. The enzymatic composition of the mitochondrial inner compartment is compared to over-all mitochondrial function. The role of the mitochondrial outer compartment is discussed with reference to both the inner membrane-matrix fraction and the intact mitochondrion.
Topics: Biological Transport; Microscopy, Electron; Mitochondria; Proteins
PubMed: 4921326
DOI: 10.1073/pnas.66.1.125 -
Microbial Genomics Nov 2023Archamoebae comprises free-living or endobiotic amoebiform protists that inhabit anaerobic or microaerophilic environments and possess mitochondrion-related organelles...
Archamoebae comprises free-living or endobiotic amoebiform protists that inhabit anaerobic or microaerophilic environments and possess mitochondrion-related organelles (MROs) adapted to function anaerobically. We compared reconstructed MRO proteomes of eight species (six genera) and found that the common ancestor of Archamoebae possessed very few typical components of the protein translocation machinery, electron transport chain and tricarboxylic acid cycle. On the other hand, it contained a sulphate activation pathway and bacterial iron-sulphur (Fe-S) assembly system of MIS-type. The metabolic capacity of the MROs, however, varies markedly within this clade. The glycine cleavage system is widely conserved among Archamoebae, except in , probably owing to its role in catabolic function or one-carbon metabolism. MRO-based pyruvate metabolism was dispensed within subgroups Entamoebidae and Rhizomastixidae, whereas sulphate activation could have been lost in isolated cases of , and sp. The MIS (Fe-S) assembly system was duplicated in the common ancestor of Mastigamoebidae and Pelomyxidae, and one of the copies took over Fe-S assembly in their MRO. In Entamoebidae and Rhizomastixidae, we hypothesize that Fe-S cluster assembly in both compartments may be facilitated by dual localization of the single system. We could not find evidence for changes in metabolic functions of the MRO in response to changes in habitat; it appears that such environmental drivers do not strongly affect MRO reduction in this group of eukaryotes.
Topics: Anaerobiosis; Mitochondria; Eukaryota; Iron; Sulfates
PubMed: 37994879
DOI: 10.1099/mgen.0.001143 -
Journal of the National Cancer Institute Jul 2000Mitochondrial membrane permeabilization is a critical event in the process leading to physiologic or chemotherapy-induced apoptosis (programmed cell death). This... (Review)
Review
Mitochondrial membrane permeabilization is a critical event in the process leading to physiologic or chemotherapy-induced apoptosis (programmed cell death). This permeabilization event is, at least in part, under the control of the permeability transition pore complex (PTPC). Oncoproteins from the Bcl-2 family and tumor suppressor proteins from the Bax family interact with PTPC to inhibit or facilitate membrane permeabilization, respectively. Conventional chemotherapeutic agents elicit mitochondrial permeabilization in an indirect fashion by induction of endogenous effectors that are involved in the physiologic control of apoptosis. However, an increasing number of experimental anticancer drugs, including lonidamine, arsenite, betulinic acid, CD437, and several amphipathic cationic alpha-helical peptides, act directly on mitochondrial membranes and/or on the PTPC. Such agents may induce apoptosis in circumstances in which conventional drugs fail to act because endogenous apoptosis induction pathways, such as those involving p53, death receptors, or apical caspase activation, are disrupted. However, stabilization of the mitochondrial membrane by antiapoptotic Bcl-2-like proteins reduces the cytotoxic potential of most of these drugs. Targeting of specific PTPC components may overcome this Bcl-2-mediated apoptosis inhibition. One strategy involves cross-linking of critical redox-sensitive thiol groups within the PTPC; another involves the use of ligands to the mitochondrial benzodiazepine receptor. Thus, the design of mitochondrion-targeted cytotoxic drugs may constitute a novel strategy for overcoming apoptosis resistance.
Topics: Animals; Antineoplastic Agents; Apoptosis; Humans; Intracellular Membranes; Mitochondria; Neoplasms; Permeability; Proto-Oncogene Proteins c-bcl-2; Signal Transduction
PubMed: 10880547
DOI: 10.1093/jnci/92.13.1042 -
Journal of Molecular and Cellular... Jan 2015This is an exciting time in mitochondrial biology. The mitochondrion is finally beginning to reveal some of its long held secrets. The scientific community has started...
This is an exciting time in mitochondrial biology. The mitochondrion is finally beginning to reveal some of its long held secrets. The scientific community has started to identify at the molecular level some of the key channels and transporters that have been well studied biochemically, but which have escaped molecular identification. This special issue provides state-of-the art reviews and original articles on the mitochondrial permeability transition pore (mPTP), regulation of mitochondrial calcium homeostasis and regulation of mitochondrial dynamics.
Topics: Humans; Mitochondria
PubMed: 25463271
DOI: 10.1016/j.yjmcc.2014.11.016 -
Recent Patents on Endocrine, Metabolic... May 2013
Topics: Animals; Cell Death; Energy Metabolism; Humans; Mitochondria
PubMed: 23432156
DOI: 10.2174/1872214811307020001