Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved

Capel, Frédéric; Rimbert, Virginie; Lioger, Delphine; Diot, Alan; Rousset, Paulette; Mirand, Philippe Patureau; Boirie‌, Yves; Morio, Béatrice; Mosoni, Laurent

doi:10.1016/j.mad.2004.11.001

Cited by 96 publications

(82 citation statements)

References 24 publications

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“…Consistent with the hypothesis that mitochondrial changes are important in sarcopenia, numerous studies have identified increases in ROS production (Capel et al, 2005;Muller et al, 2007;Chabi et al, 2008) and altered function of the mPTP (Chabi et al, 2008;Seo et al, 2008;Picard et al, 2010) in aging muscle. In addition, several mechanisms have been proposed to account for an accumulation of mitochondria with impaired function in aging muscle, including mitochondrial DNA damage (Wanagat et al, 2001;Hiona et al, 2010), reduced mitochondrial protein turnover resulting from both reduced mitochondrial degradation and reduced synthesis of new mitochondria (Rooyackers et al, 1996;Chabi et al, 2008;Ljubicic & Hood, 2009), and mitochondrial iron accumulation leading to an exacerbation of mitochondrial oxidative stress (Seo et al, 2008).…”

Section: Introductionmentioning

confidence: 55%

Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles

et al. 2011

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SummaryTo determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H 2 O 2 emission, and function of the mitochondrial permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age-related atrophy. Muscle atrophy with aging was greatest in fast-twitch gastrocnemius (Gas) muscle ()38%), intermediate in both the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles ()21%), and non-existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H 2 O 2 emission per O 2 flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age-related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy.

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Section: Introductionmentioning

confidence: 55%

Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles

et al. 2011

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“…Indeed, rising levels of matrix calcium favors mitochondrial ROS release (Martin et al 2007) through a mechanism that can imply succinate accumulation (Sentex et al 1999). Succinate-ubiquinone reductase (complex II) reoxidizes succinate, which can support important ROS production at the level of complex I via reverse electron flux (Capel et al 2005;Lacraz et al 2008). This mechanism is probably responsible for the huge ROS production that transitorily occurs at early reperfusion in the adult heart (Demaison et al 2001), which is most likely amplified in the aging heart.…”

Section: Introductionmentioning

confidence: 99%

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

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Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10-or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H 2 O 2 release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H 2 O 2 when they oxidize FADH 2 -linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration AGE (2011) of the coronary perfusion was explained by an increased mitochondrial ROS release related to the preservation of complex II activity during reperfusion.

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“…En lien avec cette théorie, de multiples études, réalisées par la suite, s'accordèrent sur le fait que le vieillissement musculaire était associé à une augmentation de marqueurs du stress oxydant [13][14][15][16][17]. Plusieurs études ont également rapporté une augmentation de la production d'EAO par les mitochondries musculaires au cours du vieillissement chez l'homme [18,19], chez de la vitesse maximale de consommation d'oxygène, que ce soit chez l'homme [29][30][31], le rat [32][33][34][35][36], ou chez la souris [20,37]. Conley et al ont ainsi observé que le fonctionnement intrinsèque des mitochondries (c'est-à-dire leur capacité de respiration maximale) était altéré avec le vieillissement musuclaire [31].…”

Section: Mitochondries Et Vieillissement Musculaireunclassified

Dysfonctions mitochondriales et vieillissement musculaire

et al. 2017

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Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved

Cited by 96 publications

References 24 publications

Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles

Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Dysfonctions mitochondriales et vieillissement musculaire

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