Mitochondrial Myopathy Studies on Permeabilized Muscle Fibers1

Letellier, Thierry; Malgat, Monique; Coquet, M; Moretto, Brigitte; Parrot-Roulaud, F.; Mazat, Jean‐Pierre

doi:10.1203/00006450-199207000-00004

Cited by 87 publications

(54 citation statements)

References 9 publications

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“…The heart was quickly excised and placed in an ice-cold BIOPS relaxing solution containing 10 mmol l −1 Ca-EGTA buffer, 0.1 µM free Ca 2+ , 20 mmol l −1 imidazole, 20 mmol l −1 taurine, 50 mmol l −1 K-MES, 0.5 mmol l −1 dithiothreitol, 6.56 mmol l −1 MgCl 2 , 5.77 mmol l −1 ATP, 15 mmol l −1 phosphocreatine, pH 7.1 (Veksler et al, 1987;Letellier et al, 1992) before further dissection. The heart was then emptied of blood, the bulbus and atrium removed, and the ventricle was weighed and cut into three parts.…”

Section: Materials and Methods Experimental Animals Temperature Protmentioning

confidence: 99%

Dynamic changes in cardiac mitochondrial metabolism during warm acclimation in rainbow trout

Pichaud

Ekström

Hellgren

et al. 2017

Journal of Experimental Biology

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Although the mitochondrial metabolism responses to warm acclimation have been widely studied in fish, the time course of this process is less understood. Here, we characterized the changes of rainbow trout (Oncorhynchus mykiss) cardiac mitochondrial metabolism during acute warming from 10 to 16°C, and during the subsequent warm acclimation for 39 days. We repeatedly measured mitochondrial oxygen consumption in cardiac permeabilized fibers and the functional integrity of mitochondria (i.e. mitochondrial coupling and cytochrome c effect) at two assay temperatures (10 and 16°C), as well as the activities of citrate synthase (CS) and lactate dehydrogenase (LDH) at room temperature. LDH and CS activities significantly increased between day 0 (10°C acclimated fish) and day 1 (acute warming to 16°C) while mitochondrial oxygen consumption measured at respective in vivo temperatures did not change. Enzymatic activities and mitochondrial oxygen consumption rates significantly decreased by day 2, and remained stable during warm acclimation (days 2-39). The decrease in rates of oxygen between day 0 and day 1 coincided with an increased cytochrome c effect and a decreased mitochondrial coupling, suggesting a structural/ functional impairment of mitochondria during acute warming. We suggest that after 2 days of warm acclimation, a new homeostasis is reached, which may involve the removal of dysfunctional mitochondria. Interestingly, from day 2 onwards, there was a lack of differences in mitochondrial oxygen consumption rates between the assay temperatures, suggesting that warm acclimation reduces the acute thermal sensitivity of mitochondria. This study provides significant knowledge on the thermal sensitivity of cardiac mitochondria that is essential to delineate the contribution of cellular processes to warm acclimation.

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Section: Materials and Methods Experimental Animals Temperature Protmentioning

confidence: 99%

Dynamic changes in cardiac mitochondrial metabolism during warm acclimation in rainbow trout

Pichaud

Ekström

Hellgren

et al. 2017

Journal of Experimental Biology

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“…After 15-20 min of permeabilization,[60% of the cytosolic lactate dehydrogenase was released from the muscle fibres, while the mitochondrial citrate synthase activity remained\5% in the supernatant. 8,9 Mitochondrial function was quantified by measuring adenosine diphosphate-stimulated oxygen consumption (State 3 respiration) polarographically at 30°C using a Clark-type electrode (Strathkelvin Instruments, Glasgow, UK) connected to a personal computer that displayed the respiration rate value online (949 oxygen System, Strathkelvin Instruments). Adenosine diphosphate-stimulated oxygen consumption reflects the first derivative of the oxygen concentration in time in the respiration chamber and is termed oxygen flux corrected for wet weight muscle tissue (2-5 mg) introduced into the chamber.…”

Section: Rat Modelmentioning

confidence: 99%

Time course of mitochondrial metabolism alterations to repeated injections of bupivacaine in rat muscle

Nouette‐Gaulain

Bringuier

Canal-Raffin

et al. 2010

Can J Anesth/J Can Anesth

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Purpose Bupivacaine-induced myotoxicity is associated with mitochondrial bioenergetic alterations. The impact of the duration of bupivacaine treatment on mitochondrial energy production remains undetermined. Here, we assessed, in vivo, the alteration of mitochondrial metabolism following different durations of bupivacaine exposure (40, 56, or 112 hr) that correspond to 5, 7, or 14 repeated injections of 0.25% bupivacaine, respectively. Methods Rats were divided randomly into seven different groups: one control group (no catheter); three groups with normal saline injections (1 mLÁkg -1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr, respectively; and three groups with 0.25% bupivacaine injections(1 mLÁkg -1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr. Psoas and gracilis muscle samples located within the bupivacaine infusion-diffusion space were investigated. To estimate mitochondrial respiratory capacity, the protein content of the mitochondrial respiratory chain apparatus was evaluated by measuring citrate synthase activity. To measure mitochondrial respiratory function, adenosine diphosphate-stimulated oxygen consumption was measured by polarography in saponinskinned muscle fibres using glutamate-malate or succinate as energy substrates. Results In psoas and gracilis muscles, saline solution had no effect on the two mitochondrial parameters. Bupivacaine induced a significant decrease in the citrate synthase activity in psoas (r 2 = 0.74; P \ 0.001) and gracilis muscle (r 2 = 0.52; P \ 0.001), and there was a significant decrease in the adenosine diphosphatestimulated oxygen consumption using glutamate or succinate as substrates in both muscles (P \ 0.001). Conclusions The severity of bupivacaine-induced myotoxicity is closely linked to the duration of bupivacaine exposure in the muscle fibres located close to the catheter tip. RésuméObjectif La myotoxicite´induite par bupivacaı¨ne est associe´e à des alte´rations du me´tabolisme e´nerge´tique mitochondrial. Nous ne connaissons pas l'impact de la dure´e d'un traitement de bupivacaı¨ne sur la production e´nerge´tique mitochondriale. Dans cette e´tude, nous avons e´value´in vivo l'alte´ration du me´tabolisme mitochondrial al a suite de diffe´rentes dure´es d'exposition a`la bupivacaı¨ne (40, 56 ou 112 h), ce qui correspond respectivement a`cinq, sept ou 14 injections re´pe´te´es de bupivacaı¨ne a`0,25 %. Méthode Les rats ont e´te´randomise´s en sept groupes diffe´rents: un groupe te´moin (pas de cathe´ter); trois groupes avec des injections de se´rum physiologique (1 mLÁkg -1 ) toutes les huit heures via un cathe´ter au niveau du nerf fe´moral pendant 40, 56 et 112 h, respectivement; et trois groupes recevant des injections de bupivacaı¨ne a`0,25 % (1 mLÁkg -1 ) toutes les huit heures via un cathe´ter au niveau du nerf fe´moral pendant 40, 56 et 112 h. Des e´chantillons du muscle psoas et du muscle gracilis situe´s dans l'espace de diffusion de la bupivacaı¨ne ont e´te´examine´s. Le contenu prote´inique ...

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“…For instance, we have shown that as low as 30% of the cytochrome c oxidase (COX) activity is sufficient to maintain a normal respiratory rate (Letellier et al, 1992(Letellier et al, , 1993(Letellier et al, , 1994Rossignol et al, 1999). Thus, it is difficult to demonstrate the presence of a deficit in a respiratory chain complex from the polarographic study.…”

Section: Mitochondrial Diseases Statistical Analysismentioning

confidence: 99%

“…Oxygen consumption rate was measured polarographically at 30°C on permeabilized muscle fibers as described in Letellier et al (1992). The respiratory activities (Resp.…”

Section: Biochemical Studymentioning

confidence: 99%

“…Our biochemical assays on crude muscle homogenates or on permeabilized muscle fibers resulted in a set of eleven enzymatic and polarographic parameters (Letellier et al, 1992). A combination of some of these parameters, mainly for standardization, by citrate synthase (CS), succinate dehydrogenase (SDH) or protein concentration in a crude homogenate (CP), improves the overall understanding of the set.…”

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Statistical Analysis of Mitochondrial Pathologies in Childhood: Identification of Deficiencies Using Principal Component Analysis

Letellier¹,

Durrieu²,

Malgat³

et al. 2000

Laboratory Investigation

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SUMMARY:Mitochondrial pathologies are a heterogeneous group of metabolic disorders that are frequently characterized by anomalies of oxidative phosphorylation, especially in the respiratory chain. The identification of these anomalies may involve many investigations, and biochemistry is a main tool. However, considering the whole set of biochemical data, the interpretation of the results by the traditionally used statistical methods remains complex and does not always lead to an unequivocal conclusion about the presence or absence of a respiratory chain defect. This arises from three main problems: (a) the absence of an a priori-defined control population, because the determination of the control values are derived from the whole set of investigated patients, (b) the small size of the population studied, (c) the large number of variables collected, each of which creates a wide variability. To cope with these problems, the principal component analysis (PCA) has been applied to the biochemical data obtained from 35 muscle biopsies of children suspected of having a mitochondrial disease. This analysis makes it possible for each respiratory chain complex to distinguish between different subsets within the whole population (normal, deficient, and, in between, borderline subgroups of patients) and to detect the most discriminating variables. PCA of the data of all complexes together showed that mitochondrial diseases in this population were mainly caused by multiple deficits in respiratory chain complexes. This analysis allows the definition of a new subgroup of newborns, which have high respiratory chain complex activity values. Our results show that the PCA method, which simultaneously takes into account all of the concerned variables, allows the separation of patients into subgroups, which may help clinicians make their diagnoses. (Lab Invest 2000, 80:1019-1030.

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Mitochondrial Myopathy Studies on Permeabilized Muscle Fibers1

Cited by 87 publications

References 9 publications

Dynamic changes in cardiac mitochondrial metabolism during warm acclimation in rainbow trout

Dynamic changes in cardiac mitochondrial metabolism during warm acclimation in rainbow trout

Time course of mitochondrial metabolism alterations to repeated injections of bupivacaine in rat muscle

Statistical Analysis of Mitochondrial Pathologies in Childhood: Identification of Deficiencies Using Principal Component Analysis

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