scholarly journals Complex I and ATP Content Deficiency in Lymphocytes from Friedreich's Ataxia

2009 ◽  
Vol 36 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Mohammad Mehdi Heidari ◽  
Massoud Houshmand ◽  
Saman Hosseinkhani ◽  
Shahriar Nafissi ◽  
Mehri Khatami
Keyword(s):  
Respiratory Chain ◽  
Complex I ◽  
Age Of Onset ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Iron Accumulation ◽  
Atp Content ◽  
Respiratory Chain Complexes ◽  
Intracellular Atp ◽  
Complex I Activity

Background:Friedreich's ataxia (FRDA) is an inherited recessive disorder characterized by progressive neurological disability and heart abnormalities. A deficiency in the protein frataxin causes this disease. Frataxin deficiency leads to progressive iron accumulation in mitochondria, excessive free radical production and dysfunction of respiratory chain complexes. The expansion (GAA) repeat in the first intron causes decreased frataxin expression by interfering with transcription.Methods:Activity of mitochondrial respiratory chain complex I (measured as NADH ferricyanide reductase) and intracellular ATP measurement was performed on lymphocyte of FRDA patients (n=12) and control subjects (n=25).Results:Our findings showed that complex I activity and intracellular ATP were significantly reduced (P=0.001) in patients compared with controls and we found strong correlation between complex I activity and intracellular ATP content in FRDA patients (r = 0.93; P<0.002). 8.6 and 9.0 kb deletion in mtDNA was detected in 9 patients out of 12 (75%) by multiplex polymerase chain reaction (PCR) and Southern blot analysis.Conclusions:This study suggested that a biochemical defect in complex I activity and ATP production, which may be due to iron accumulation in mitochondria, can be involved in age of onset of FRDA.

scholarly journals Global ischaemia induces a biphasic response of the mitochondrial respiratory chain. Anoxic pre-perfusion protects against ischaemic damage

1992 ◽  
Vol 281 (3) ◽  
pp. 709-715 ◽  
Author(s):  
K Veitch ◽  
A Hombroeckx ◽  
D Caucheteux ◽  
H Pouleur ◽  
L Hue
Keyword(s):  
Respiratory Chain ◽  
Complex I ◽  
Nadh Oxidase ◽  
Mitochondrial Respiratory Chain ◽  
Complex Iii ◽  
Biphasic Response ◽  
Ischaemic Damage ◽  
Global Ischaemia ◽  
Complex I Activity ◽  
Mitochondrial Respiratory

Studies of Langendorff-perfused rat hearts have revealed a biphasic response of the mitochondrial respiratory chain to global ischaemia. The initial effect is a 30-40% increase in the rate of glutamate/malate oxidation after 10 min of ischaemia, owing to an increase in the capacity for NADH oxidation. This effect is followed by a progressive decrease in these oxidative activities as the ischaemia is prolonged, apparently owing to damage to Complex I at a site subsequent to the NADH dehydrogenase component. This damage is exacerbated by reperfusion, which causes a further decrease in Complex I activity and also decreases the activities of the other complexes, most notably of Complex III. Perfusion for up to 1 h with anoxic buffer produced only the increase in NADH oxidase activity, and neither anoxia alone, nor anoxia and reperfusion, caused loss of Complex I activity. Perfusing for 3-10 min with anoxic buffer before 1 h of global ischaemia had a significant protective effect against the ischaemia-induced damage to Complex I.

scholarly journals Blood-based mitochondrial respiratory chain function in major depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Johan Fernström ◽  
Synthia H. Mellon ◽  
Marlon A. McGill ◽  
Martin Picard ◽  
Victor I. Reus ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Complex I ◽  
Mononuclear Cells ◽  
Rating Scale ◽  
Citrate Synthase ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Markers ◽  
Mitochondrial Dna Copy Number ◽  
Complex I Activity ◽  
Mitochondrial Respiratory

AbstractMitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.

scholarly journals Effects of Xingpi Kaiyu Fang on ATP, Na/K-ATPase, and Respiratory Chain Complexes of Hippocampus and Gastrocnemius Muscle in Depressed Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Qingjie Yuan ◽  
Yang Li ◽  
Xiaofei Deng ◽  
Huawei Shi ◽  
Zhenwu Zhao ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Respiratory Chain ◽  
Gastrocnemius Muscle ◽  
Chain Complex ◽  
Respiratory Chain Complex ◽  
Atp Content ◽  
Mitochondrial Ultrastructure ◽  
Respiratory Chain Complexes ◽  
Chain Complexes ◽  
Ultrastructural Damage

Objective. To clarify the effectiveness and mechanism of the Chinese herbal formula Xingpi Kaiyu Fang (XPKYF) which is composed of American ginseng (Xi-Yang-shen), Radix curcumae (Yu-Jin), Acori tatarinowii rhizoma (Shi-Chang-pu), and Hypericum perforatum (Guan-Ye-lian-qiao) in depressed rats. Methods. The rat model of depression was established by chronic unpredictable mild stress (CUMS) method for 6 weeks. Rats were randomly divided into six groups: control group, CUMS group, CUMS+XPKYF (3.6g/kg/d, 7.2g/kg/d, 14.4g/kg/d) groups, and CUMS+sertraline (4.5mg/kg/d) group. The sucrose preference test and the forced swimming test were performed to assess the rats’ depression behavior. Mitochondrial ultrastructure was observed by transmission electron microscope and adenosine triphosphate (ATP) content, sodium potassium ATPase (Na/K-ATPase) activity, and mitochondrial respiratory chain complexes activities in hippocampus and gastrocnemius muscle were measured at the 14th and 42nd day. Results. Rats subjected to six weeks of CUMS exhibited decreased sucrose preference ratio and prolonged immobility time. CUMS reduced ATP content in hippocampus, decreased Na/K-ATPase activity and respiratory chain complex I, III, and IV activities in hippocampus and gastrocnemius muscle, and damaged mitochondrial ultrastructure of hippocampus and gastrocnemius muscle. XPKYF at 14.4g/kg, the efficacy trend of which was better than the other drug groups, could prevent the stress-induced depressed behavior changes, inhibit the decrease of Na/K-ATPase activity in hippocampus, inhibit the decrease of respiratory chain complex III activities in hippocampus and gastrocnemius muscle, and protect mitochondria from ultrastructural damage. Conclusions. Energy deficiency and damaged mitochondrial ultrastructure were found in hippocampus and gastrocnemius muscle of depressed rats established by CUMS. XPKYF could partly reverse alterations in ATP, Na/K-ATPase, and respiratory chain complexes of hippocampus and gastrocnemius muscle and protect mitochondria from ultrastructural damage. This provides another experimental evidence for the clinical application of XPKYF in the treatment of depression.

scholarly journals Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases

2001 ◽  
Vol 56 (5) ◽  
pp. 143-148 ◽  
Author(s):  
Lilian M. J. Albano ◽  
Mayana Zatz ◽  
A. Kim Chong ◽  
Débora Bertola ◽  
Sofia M. M. Sugayama ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Age At Onset ◽  
Cranial Nerves ◽  
Autosomal Recessive Inheritance ◽  
Molecular Study ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Gaa Expansion ◽  
Neurologic Findings

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

scholarly journals Conserved in situ arrangement of complex I and III2 in mitochondrial respiratory chain supercomplexes of mammals, yeast, and plants

2018 ◽  
Vol 115 (12) ◽  
pp. 3024-3029 ◽  
Author(s):  
Karen M. Davies ◽  
Thorsten B. Blum ◽  
Werner Kühlbrandt
Keyword(s):  
Respiratory Chain ◽  
Complex I ◽  
Principal Component ◽  
Complex Iii ◽  
Asparagus Officinalis ◽  
Mutual Arrangement ◽  
Inner Mitochondrial Membrane ◽  
Respiratory Chain Complexes ◽  
Complex Iv

We used electron cryo-tomography and subtomogram averaging to investigate the structure of complex I and its supramolecular assemblies in the inner mitochondrial membrane of mammals, fungi, and plants. Tomographic volumes containing complex I were averaged at ∼4 nm resolution. Principal component analysis indicated that ∼60% of complex I formed a supercomplex with dimeric complex III, while ∼40% were not associated with other respiratory chain complexes. The mutual arrangement of complex I and III2 was essentially conserved in all supercomplexes investigated. In addition, up to two copies of monomeric complex IV were associated with the complex I1III2 assembly in bovine heart and the yeast Yarrowia lipolytica, but their positions varied. No complex IV was detected in the respiratory supercomplex of the plant Asparagus officinalis. Instead, an ∼4.5-nm globular protein density was observed on the matrix side of the complex I membrane arm, which we assign to γ-carbonic anhydrase. Our results demonstrate that respiratory chain supercomplexes in situ have a conserved core of complex I and III2, but otherwise their stoichiometry and structure varies. The conserved features of supercomplex assemblies indicate an important role in respiratory electron transfer.

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