Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

AbstractOur current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

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Relationships between the activity of respiratory-chain complexes in pre- (biopsy) or post-slaughter muscle samples and feed efficiency in random-bred Ghezel lambs

Animal Production Science ◽

10.1071/an15184 ◽

2017 ◽

Vol 57 (8) ◽

pp. 1674

Author(s):

M. J. Zamiri ◽

R. Mehrabi ◽

G. R. Kavoosi ◽

H. Rajaei Sharifabadi

Keyword(s):

Respiratory Chain ◽

Feed Intake ◽

Enzyme Activities ◽

Feed Efficiency ◽

Average Daily Gain ◽

Chain Complex ◽

Respiratory Chain Complex ◽

Respiratory Chain Complexes ◽

Chain Complexes ◽

Daily Gain

The present study was conducted to determine the relationship between the activity of mitochondrial respiratory chain complexes in pre- and post-slaughter muscle samples and residual feed intake (RFI) in Ghezel male lambs born as a result of random mating. The study was based on the hypothesis that random-bred lambs with lower feed (or higher) RFI have lower (or higher) respiratory chain-complex activity in muscle samples. Lambs (n = 30) were fed a diet consisting of 70% concentrate and 30% alfalfa hay during a 70-day period. Individual feed intake and average daily gain were recorded to calculate the RFI, feed-conversion ratio (FCR) and adjusted FCR (aFCR). On the basis of these calculations, the lambs were classified into low and high groups for RFI, with FCR and aFCR (n = 22) being one standard deviation above or below the means; this was corroborated by Student’s t-test (P < 0.01). At the end of the experiment, a 10-g biopsy sample was taken from the posterior side of the left femoral biceps. After 24 h, the lambs were slaughtered, and a sample from the posterior side of the right femoral biceps was dissected for determination of mitochondrial protein and respiratory chain-complex activities (Complexes I–V). The RFI was not correlated with the metabolic bodyweight and average daily gain, but was positively correlated (r = 0.56) with the average daily feed intake (P < 0.01); mean daily feed intake in the low-RFI group was 200 g less than that in the high-RFI group. The FCR and aFCR were not significantly (P > 0.05) correlated with average daily feed intake (r = 0.39 and r = 0.36 respectively), but showed a negative correlation (P < 0.01) with average daily gain (r = –0.73 and r = –0.76 respectively). Although very high negative correlations were recorded between the activities of all five respiratory-chain complexes and RFI in muscle samples obtained before (–0.91 to –0.97) and after (–0.92 to –0.97) slaughter, Complexes I and V showed small negative correlations (–0.40) with FCR or aFCR (P < 0.05). Enzyme activities of the respiratory-chain Complexes I, III and V were not significantly different between the pre- and post-slaughter biopsy samples; however, the enzyme activities of respiratory-chain Complexes II and IV were slightly higher in post-slaughter samples (P < 0.01). These results suggested that it may be possible to use the enzymatic activity of respiratory-chain complexes in muscle biopsy samples for screening of lambs for RFI, providing a useful procedure for genetic selection of lambs for this component of feed efficiency. These encouraging results need to be verified in further experiments using other sheep breeds and a larger number of lambs.

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Effect of inhibitors of mitochondrial respiratory chain complexes on the electromechanical activity in human myocardium

Medicina ◽

10.3390/medicina46100096 ◽

2010 ◽

Vol 46 (10) ◽

pp. 679

Author(s):

Vida Gendvilienė ◽

Irma Martišienė ◽

Danguolė Zablockaitė ◽

Jonas Jurevičius

Keyword(s):

Respiratory Chain ◽

Control Level ◽

Chain Complex ◽

Mitochondrial Respiratory Chain ◽

Human Myocardium ◽

Contraction Force ◽

Respiratory Chain Complexes ◽

Complex Iv ◽

Resting Tension ◽

Chain Complexes

The aim of the study was to investigate the effect of inhibitors of mitochondrial respiratory chain complexes I, III, and IV on the electromechanical activity in human myocardium. Material and methods. The experiments were performed on the human myocardial strips obtained from patients with heart failure (NYHA class III or IV) using a conventional method of registration of myocardial electromechanical activity. Under the perfusion with physiological Tyrode solution (control), contraction force (P) was 0.94±0.12 mN (n=16), relaxation time (t50) was 173.38±5.03 ms (n=15), action potential durations measured at 50% (AP50) and 90% (AP90) repolarization were 248.96±13.38 ms and 398.59±17.93 ms, respectively (n=13). Results. The inhibition of respiratory chain complex I by rotenone (3×10–5 M, the highest concentration applied) decreased contraction force of human myocardium to 48.99%±14.74% (n=3) (P<0.05); AP50, to 81.34%±15.81%; and AP90, to 87.28%±7.25% (n=3) (P>0.05) of control level, while relaxation time and resting tension remained almost unchanged. Antimycin A, an inhibitor of complex III, applied at the highest concentration (3×10–4 M) reduced P to 41.66%±8.8% (n=5) (P<0.001) and marginally increased t50 and decreased the durations of AP. Anoxia (3 mM Na2S2O4) that inhibits the activity of complex IV reduced the contraction force to 9.23%±3.56% (n=6) (P<0.001), AP50 and AP90 to 65.46%±9.95% and 71.07%±8.39% (n=5) (P<0.05) of control level, respectively; furthermore, the resting tension augmented (contracture developed). Conclusions. Our results show that the inhibition of respiratory chain complex IV had the strongest inhibitory effect on the electromechanical activity of failing human myocardium.

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AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress

Blood ◽

10.1182/blood-2014-08-594408 ◽

2015 ◽

Vol 125 (13) ◽

pp. 2120-2130 ◽

Cited By ~ 104

Author(s):

Shrivani Sriskanthadevan ◽

Danny V. Jeyaraju ◽

Timothy E. Chung ◽

Swayam Prabha ◽

Wei Xu ◽

...

Keyword(s):

Respiratory Chain ◽

Metabolic Stress ◽

Chain Complex ◽

Reserve Capacity ◽

Respiratory Chain Complex ◽

Respiratory Chain Complexes ◽

Mitochondrial Mass ◽

Chain Complexes ◽

Key Points ◽

Complex Activities

Key Points AML cells have increased mitochondrial mass, low respiratory chain complex activities, and low spare reserve capacity compared with normal cells. AML cells have heightened sensitivity to inhibitors of the respiratory chain complexes and oxidative stressors.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6054926 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

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.

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Ultrastructural and functional abnormalities of mitochondria in cultivated fibroblasts from α-mannosidosis patients

Biologia ◽

10.2478/s11756-009-0054-2 ◽

2009 ◽

Vol 64 (2) ◽

Cited By ~ 2

Author(s):

Olga Brantova ◽

Befekadu Asfaw ◽

Jana Sladkova ◽

Helena Poupetova ◽

Jan Zivny ◽

...

Keyword(s):

Respiratory Chain ◽

Energy Demand ◽

Citrate Synthase ◽

Chain Complex ◽

Lysosomal Storage ◽

Respiratory Chain Complexes ◽

Gene Encoding ◽

Chain Complexes ◽

Ultrastructure And Function ◽

And Function

Abstractα-Mannosidosis is a lysosomal storage disorder caused by α-mannosidase deficiency. Clinical course of the disease ranges from severe infantile to milder juvenile type and includes mental retardation, skeletal deformities, coarse facies, hepatomegaly and hearing loss. The aim of the study was to analyse mitochondrial ultrastructure and function in cultivated fibroblasts from three patients with α-mannosidosis. All patients were homozygous for the c.2248C>T mutation in the MAN2B1 gene encoding lysosomal α-mannosidase. The mutation results in incorrect protein folding and severe decrease of α-mannosidase activity. The misfolded protein is retained by the control system of endoplasmic reticulum (ER). In analysed fibroblasts, we observed dilated ER, higher amount of aberrant mitochondria and reduced mitochondrial mass compared to controls. Respiratory chain complex IV, cytochrome c oxidase (COX), activity and the ratio between COX and citrate synthase (control enzyme) were significantly increased in comparison to controls (P < 0.05). Furthermore, the activity at least from one of other respiratory chain complexes was increased in each studied cell line. Mitochondrial membrane potential as well as reactive oxygen species production were comparable with controls. Based on our results, we hypothesize more profound effect of swelled and damaged mitochondria and ER dilatation on tissues with higher energy demand than fibroblasts have.

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Enzymatic activities linked to cardiac energy metabolism of Trypanosoma evansi-infected rats and their possible functional correlations to disease pathogenesis

Parasitology ◽

10.1017/s0031182015000220 ◽

2015 ◽

Vol 142 (9) ◽

pp. 1163-1170 ◽

Cited By ~ 11

Author(s):

MATHEUS D. BALDISSERA ◽

VIRGINIA C. RECH ◽

MATEUS GRINGS ◽

LUCAS T. GRESSLER ◽

RODRIGO A. VAUCHER ◽

...

Keyword(s):

Energy Metabolism ◽

Cardiac Function ◽

Respiratory Chain ◽

Heart Function ◽

Chain Complex ◽

Trypanosoma Evansi ◽

Enzymatic Activities ◽

Phosphoryl Transfer ◽

Respiratory Chain Complexes ◽

Chain Complexes

SUMMARYThe aim of this study was to investigate the activities of important enzymes involved in the phosphoryl transfer network (adenylate kinase and creatine kinase (CK)), lactate dehydrogenase (LDH), respiratory chain complexes and biomarkers of cardiac function in rat experimentally infected by Trypanosoma evansi. Rat heart samples were evaluated at 5 and 15 days post-infection (PI). At 5 day PI, there was an increase in LDH and CK activities, and a decrease in respiratory chain complexes II, IV and succinate dehydrogenase activities. In addition, on day 15 PI, a decrease in the respiratory chain complex IV activity was observed. Biomarkers of cardiac function were higher in infected animals on days 5 and 15 PI. Considering the importance of the energy metabolism for heart function, it is possible that the changes in the enzymatic activities involved in the cardiac phosphotransfer network and the decrease in respiratory chain might be involved partially in the role of biomarkers of cardiac function of T. evansi-infected rats.

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