This article reviews the structure and function of mitochondrial respiratory chain complex Ⅱ, and the clinical features, diagnosis, treatment and genetic analysis of mitochondrial respiratory chain complex Ⅱ deficiency. Mitochondrial complex Ⅱ, known as succinate dehydrogenase, is a part of the mitochondrial respiratory chain. It plays an important role in cellular oxidative phosphorylation. It is associated with oxidative stress and is a sensitive target for toxic substances and abnormal metabolin in cells. Clinical manifestations of respiratory chain complex Ⅱ deficiency are characterized by a wide variety of abnormalities. Progressive neuromuscular dysfunction is the most common syndrome. Cardiomyopathy, episodic vomit and hemolytic uremic syndrome are also encountered in a few cases. A precise diagnosis is dependent on enzyme activities assay of respiratory chain complexes and genetic analysis. Complex Ⅱ activities decreased in affected tissues. Pathogenic mutations in SDHA gene and SDHAF1 gene encoding assembly factor have been found so far. Clinical treatment aims at improving the mitochondrial function.
Animals ; Electron Transport Complex II ; chemistry ; deficiency ; physiology ; Female ; Humans ; Male ; Mitochondrial Diseases ; diagnosis ; genetics ; therapy

OBJECTIVETo explore activity laws of mitochondrial complex II in patients of deficiency-cold syndrome (DCS) and deficiency-heat syndrome (DHS) under various ambient temperatures.

METHODSSubjects were recruited by questionnaire and expert diagnosis from grade 1 - 3 undergraduates at Henan College of Traditional Chinese Medicine in November 2012, and assigned to a normal control group, the DCS group, and the DHS group, 20 in each group. Their venous blood samples were collected at two different temperature conditions. Activities of mitochondrial complex II were measured by spectrophotometry.

RESULTS(1) Comparison of mitochondrial complex It under various ambient temperatures: Compared with room temperature in the same group, activity values were all increased in the normal control group at cold temperature with significant difference (P <0.05), but there was no significant difference in the DCS group and the DHS group (P >0. 05). Compared with the normal control group, activity values of complex H were reduced in the DCS group at cold and room temperatures with significant difference (P <0.05). Compared with the DCS group, activity values of complex It were increased in the DHS group with significant difference (P <0. 05). (2) Changes of adjustment rates: Compared with room temperature, the adjustment rate all rose at cold temperature in the normal control group and the DHS group with significant difference (P <0.05), but with no significant difference found in the DCS group (P >0. 05). Compared with the normal control group at the same temperature, the adjustment rate in the DHS group and the DCS group was all reduced at cold and room temperatures with significant difference (P <0. 05). There were no significant difference in the adjustment rate between the DHS group and the DCS group (P > 0. 05).

CONCLUSIONSEnvironment temperature can affect the activity of mitochondrial complex II with different influence degrees on different syndrome types of people, but its change trend are basically identical.

Cold Temperature ; Electron Transport Complex II ; metabolism ; Hot Temperature ; Humans ; Medicine, Chinese Traditional ; Syndrome ; Temperature

OBJECTIVETo study the clinical and enzymological characteristics of the children with mitochondrial respiratory chain complex III deficiency.

METHODThe clinical manifestations of five patients (3 males, 2 females) were summarized. Spectrophotometric assay was used for the analysis of respiratory chain complex I to V enzyme activity in peripheral blood leukocytes, after obtaining venous blood.

RESULT(1) Five patients were hospitalized at the age of 1 month to 15 years. Three patients had Leigh syndrome with progressive motor developmental delay or regression and weakness. One had severe liver damage and intrahepatic cholestasis. One presented muscle weakness. (2) Deficient complex I + III activity was identified in five patients. Their complex I + III activities in peripheral blood leukocytes were 3.0 to 14.2 nmol/min per mg mitochondrial protein (control: 84.4 ± 28.5 nmol/min per mg mitochondrial protein). The ratio of complex I + III to citrate synthase decreased to 3.5 to 22.9% (normal control 66.1 ± 14.7%). The activities of complex III decreased to 10.4 to 49.3% of the lowest control value, while complex I, II, IV and V activities were normal. The results supported the diagnosis of isolated respiratory chain complex III deficiency.

CONCLUSIONComplex III deficiency is a kind of disorder of energy metabolism with various manifestations. The complex I + III activities and the ratio of complex I + III to citrate synthase were lower than those of the control. The activities of complex I, II, IV and V were normal.

Adolescent ; Child ; Child, Preschool ; Electron Transport Complex I ; metabolism ; Electron Transport Complex II ; metabolism ; Electron Transport Complex III ; metabolism ; Female ; Humans ; Infant ; Leigh Disease ; Leukocytes, Mononuclear ; enzymology ; Male ; Mitochondrial Diseases ; diagnosis ; metabolism ; physiopathology

OBJECTIVETo investigate the mechanisms of Yinxing Pingchan recipe (YXPC) and its components, i.e. the components for detoxicating (A), for calming liver (B) and for dissolving blood stasis(C), in preventing and treating Parkinson's disease, and the path of its inhibition on nigrostriatal dopaminergic neuron (DAn) apoptosis in model mice of Parkinson's disease.

METHODSMale C57BL/6J mice were divided into the normal group, the model group and four Chinese medicinal groups, that is, the YXPC group, and Group A, B and C, treated with YXPC and its components A, B and C respectively. Mouse model of Parkinson's disease was established by intraperitoneal injection with 1-methl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP). All mice were sacrificed in 2 batches at the 14th and the 28th day respectively. The activity of mitochondrial enzyme complex I, II and IV (MEC I, II and IV) in the brain of mice were measured, respectively.

RESULTSAs compared with the normal group, the activity of MEC I and IV in brain was significantly lower (P < 0.05 or P < 0.01), and that of MEC II had no obvious change in the model group. As compared with the model group, the activity of MEC I was significantly higher in YXPC group and Group C at the 14th day (P < 0.05), while the activity of MECII in Group A at the 14th day, Group B at the 28th day and Group C at both 14th and 28th day was significantly lower (P<0.05 or P<0.01). Activity of MEC IV in the four Chinese medicinal groups at the 14th day all significantly increased (P<0.05 or P<0.01), and retained at high level in Group B and Group C at the 28th day (P<0.05).

CONCLUSIONYXPC and its components can maintain the mitochondrial function by partial inhibiting the activity of its enzyme complex, preventing DAn apoptosis to slow down the progress of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Brain ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Electron Transport Complex I ; metabolism ; Electron Transport Complex II ; metabolism ; Electron Transport Complex III ; metabolism ; Electron Transport Complex IV ; metabolism ; Enzyme Activation ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria ; enzymology ; Parkinson Disease ; drug therapy ; enzymology ; etiology ; Random Allocation

Mitochondrial respiratory chain complex II deficiency is a rare documented cause of mitochondrial diseases. This study reported a case of Leigh syndrome due to isolated complex II deficiency. A boy presented with progressive weakness, motor regression and dysphagia after fever from the age of 8 months and hospitalized at the age of 10 months. Elevated blood levels of lactate and pyruvate were observed. Brain magnetic resonance image showed symmetrical lesions in the basal ganglia. Mitochondrial respiratory chain complex I-V activities in peripheral leukocytes were measured using spectrophotometric assay. Mitochondrial gene screening of common point mutations was performed. The complex II activity in the peripheral leukocytes decreased to 21.9 nmol/min per mg mitochondrial protein (control: 47.3±5.3 nmol/min per mg mitochondrial protein). The ratio of complex II activity to citrate synthase activity (22.1%) also decreased (control: 50.9%±10.7 %). No point mutation was found in mitochondrial DNA. The boy was diagnosed as Leigh syndrome due to isolated complex II deficiency. Psychomotor improvements were observed after the treatment. The patient is 22 months old and in a stable condition.
Diagnosis, Differential ; Electron Transport Complex II ; deficiency ; Humans ; Infant ; Leigh Disease ; diagnosis ; etiology ; therapy ; Male ; Mitochondrial Diseases ; complications

OBJECTIVETo explore changes of mitochondrial structure and functions, as well as the protection of ligustrazine in the process of myocardial hypertrophy.

METHODSNeonatal myocardial cells were isolated and cultured with angiotensin II (Ang II) for 72 or 96 h. The total protein content was detected using BCA method. The cell diameter was measured by inverted microscope, by which to reflect the proliferation situation of cardiomyocytes. The mitochondrial membrane potential (MMP) was measured by fluorescence microscope. The mitochondrial monoamine oxidase (MAO) activity was detected by spectrophotometer. The mitochondrial cytochrome oxidase (COX) activity and the mitochondrial damage percentage were detected by microplate reader, by which to reflect the damage of mitochondrial outer membrane's structure and the membranes' function. Also, cells were treated with ligustrazine and losartan and then the pharmacological effects on the mitochondrial structure and functions in the myocardial cells treated with Ang II were observed.

RESULTSAt 72 h and 96 h, when compared with the blank group, cells treated with Ang II had increased total protein content (P < 0.01) and enlarged diameter (P < 0.01). Treated with Ang II, the MAO activity and the outer membrane damage percentage of myocardial cells significantly increased (P < 0.01), and mitochondrial COX activity and the mitochondrial MMP significantly decreased (P < 0.01). Compared with the model group at the same time period, ligustrazine significantly reduced myocardial cells' total protein content and myocardial cell diameter, and significantly decreased myocardial cells' MAO activity, increased mitochondrial COX activity, improved the outer membrane damage percentage and inner membrane MMP at 72 and 96 h, all showing statistical difference (P < 0.01, P < 0.05).

CONCLUSIONSDuring the process of myocardial hypertrophy existed the damage to the mitochondrial structure and functions. Ligustrazine protected the mitochondrial structure and functions of the myocardial cells in reversing Ang II induced myocardial cell hypertrophy.

Angiotensin II ; adverse effects ; Animals ; Cardiomyopathy, Hypertrophic ; chemically induced ; metabolism ; pathology ; Cells, Cultured ; Electron Transport Complex IV ; metabolism ; Mitochondria, Heart ; drug effects ; enzymology ; Monoamine Oxidase ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; pathology ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley

This study is to investigate protective effect of safflor yellow B (SYB) against vascular endothelial cells (VECs) injury induced by angiotensin-II (Ang-II). VECs were cultured and divided into six groups: control group, Ang-II group, Ang-II + SYB (1 micromolL(-1)) group, Ang-II + SYB (10 micromolL(-1)) group, Ang-II + SYB (100 micromolL(-1)) group and Ang- II + verapamil (10 micromolL(-1)) group. Except control group, all of VECs in other groups were treated with Ang- II at the final concentration of 0.1 micromolL(-1). Mitochondria membrane potential (MMP) and free calcium concentration ([Ca2+]i) were measured by laser scanning confocal microscopy, and mitochondria complex IV activity was detected by BCA method. The levels of reactive oxygen species (ROS) in VECs were analyzed by fluorescence detector and apoptosis of VECs was observed by flow cytometer. Caspase 3 was determined by Western blotting method. Comparing with control group, Ang-II was able to increase [Ca2+]i and ROS level, decrease MMP level, inhibit complex IV activity and enhance caspase 3 activity in VECs, as a result, enhance apoptosis of VECs. But SYB could significantly reduce the result induced by Ang- II relying on different dosages (P < 0.05 or P < 0.01). SYB was able to eliminate the effect of Ang-II on VECs via regulating [Ca2+]i, mitochondrial structure and function and inhibiting apoptosis.
Angiotensin II ; adverse effects ; Antioxidants ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Carthamus tinctorius ; chemistry ; Caspase 3 ; metabolism ; Cells, Cultured ; Chalcone ; analogs & derivatives ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Electron Transport Complex IV ; metabolism ; Endothelial Cells ; cytology ; metabolism ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondrial Proton-Translocating ATPases ; metabolism ; Plants, Medicinal ; chemistry ; Reactive Oxygen Species ; metabolism ; Vasoconstrictor Agents ; adverse effects

The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC(50) ~100 μmol/L) and the significant structure-based binding affinity calculation (~94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.
Animals ; Anthelmintics ; metabolism ; pharmacology ; Binding Sites ; Crystallography, X-Ray ; Electron Transport Complex II ; drug effects ; Inhibitory Concentration 50 ; Mitochondria ; drug effects ; enzymology ; Molecular Structure ; Oxidoreductases ; antagonists & inhibitors ; chemistry ; Structure-Activity Relationship ; Swine ; Thiabendazole ; chemistry ; metabolism ; pharmacology ; Ubiquinone ; antagonists & inhibitors ; Water ; chemistry ; metabolism

Mitochondrial myopathy (MM) has been applied to muscle disease in which mitochondria have abnormal structure, function or both. To characterize the pathologic findings of MM, we examined the ultrastructural and histochemical findings of 24 cases of MM. The ultrastructures of the MM were characterized by abnormal mitochondria in number (pleoconia) and size (megaconia), and showed predominant accumulation of mitochondria in the subsarcolemmal space of myofibers in all cases. Mitochondria contained abnormally shaped cristae (concentric form and gyriform) in 79% of cases. Paracrystalline inclusion which was known to be a characteristics of MM were seen only in 7 cases (29%). Electron dense deposits were more frequently found (77%) in abnormal mitochondria of chronic progressive external opthalmoplegia and Kearn-Sayre syndrome. But, other findings were not specific for the specific clinical entities. On succinate dehydrogenase (SDH) stain, ragged red fibers (RRF) showed more intense positivity than modified Gomori-trichrome stain and definite strong reactive products were present along the periphery of myofibers which showed normal findings on modified Gomori-trichrome stain. In conclusion, ultrastructural findings such as mitochondria showing pleoconia with megaconia, and bizarre shaped cristae may be helpful for the diagnosis of MM and SDH stain is more useful for identification of RRF than modified Gomori-trichrome stains.
Coloring Agents ; Diagnosis ; Mitochondria ; Mitochondrial Myopathies* ; Succinate Dehydrogenase

Biomarkers, Tumor ; genetics ; Gastrointestinal Stromal Tumors ; diagnosis ; genetics ; Humans ; Succinate Dehydrogenase ; deficiency ; genetics