Thermoregulatory, carboxyatractylate‐sensitive uncoupling in heart and skeletal muscle mitochondria of the ground squirrel correlates with the level of free fatty acids

Brustovetsky, N.N.; Mv, Egorova; Gnutov, D.Yu.; Gogvadze, Vladimir; Mokhova, E. N.; Skulachev, Vladimir P.

doi:10.1016/0014-5793(92)80645-w

Cited by 30 publications

(22 citation statements)

References 14 publications

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“…pore formation, may be necessary. Again, as in the former mechanism, FFA may be a mediator of uncoupling since (a) mitochondrial FFA content increases during arousal of the hibernating animal [5], and (b) addition of palmitate to the mitochondria of aroused animals induces the CSA-sensitive uncoupling (see Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

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Cyclosporin A suppression of uncoupling in liver mitochondria of ground squirrel during arousal from hibernation

Brustovetsky

Gnutov

et al. 1993

FEBS Letters

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Energy coupling parameters were studied in liver mitochondria of ground squirrel during arousal from hibernation. It was found that such mitochondria become uncoupled during incubation with phosphate in a salt medium. The uncoupling was revealed by respiration rate increase and membrane potential decrease in the presence of oligomycin. Both effects were reversed by addition of cyclosporin A. Under the same in vitro conditions, mitochondria from aroused (active) animals showed no uncoupling but could be uncoupled by addition of palmitate in the cyclosporin A-sensitive fashion. It is proposed that formation ofeyclosporin A-sensitive pores can be involved in urgent heat production in arousing hibernators.

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Section: Discussionmentioning

confidence: 99%

“…Such measurements might include in vivo NMR of the high energy compounds and in situ studies of morphology of mitochondria. In this connection, one may mention that the [FFA] increase during arousal of ground squirrels was shown not only in isolated mitochondria but also in tissues [5].…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A suppression of uncoupling in liver mitochondria of ground squirrel during arousal from hibernation

Brustovetsky

Gnutov

et al. 1993

FEBS Letters

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“…Nevertheless, many of the studies in hibernators have only examined mitochondria isolated from liver, and when additional tissues have been investigated, results have been mixed. Hannon et al (22) found that respiration of skeletal muscle homogenates was depressed in hibernating arctic ground squirrels (Spermophilus parryii), whereas Brustovetsky et al (11) found that heart and skeletal muscle mitochondrial respiration was increased in hibernating compared with active arctic ground squirrels. If metabolic depression is tissue specific, this may account for the discrepancy between whole animal and mitochondrial studies, as whole animal oxygen consumption is a composite of total metabolic activity and may fail to resolve mitochondrial activity among individual tissues.…”

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confidence: 98%

Tissue-specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels

Barger

Brand

Barnes

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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A significant proportion of standard metabolic rate is devoted to driving mitochondrial proton leak, and this futile cycle may be a site of metabolic control during hibernation. To determine if the proton leak pathway is decreased during metabolic depression related to hibernation, mitochondria were isolated from liver and skeletal muscle of nonhibernating (active) and hibernating arctic ground squirrels (Spermophilus parryii). At an assay temperature of 37 degrees C, state 3 and state 4 respiration rates and state 4 membrane potential were significantly depressed in liver mitochondria isolated from hibernators. In contrast, state 3 and state 4 respiration rates and membrane potentials were unchanged during hibernation in skeletal muscle mitochondria. The decrease in oxygen consumption of liver mitochondria was achieved by reduced activity of the set of reactions generating the proton gradient but not by a lowered proton permeability. These results suggest that mitochondrial proton conductance is unchanged during hibernation and that the reduced metabolism in hibernators is a partial consequence of tissue-specific depression of substrate oxidation.

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“…Respiration rates of isolated mitochondria measured at 37°C are lower in ground squirrels during torpor in liver but not skeletal muscle compared with summer active controls (33, 50). However, there are clear indications of seasonal (i.e., summer vs. winter) metabolic cycles in hibernators that are distinct from the torpor-arousal cycle (16,51). In addition, hibernators do not feed throughout the winter but do feed throughout the summer, which could have effects on mitochondrial properties (11,67).…”

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confidence: 99%

Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen-lined ground squirrels

Brown

Chung

Belgrave

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Brown JCL, Chung DJ, Belgrave KR, Staples JF. Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen-lined ground squirrels. Am J Physiol Regul Integr Comp Physiol 302: R15-R28, 2012. First published October 12, 2011 doi:10.1152/ajpregu.00230.2011.-During hibernation, animals cycle between periods of torpor, during which body temperature (T b) and metabolic rate (MR) are suppressed for days, and interbout euthermia (IBE), during which T b and MR return to resting levels for several hours. In this study, we measured respiration rates, membrane potentials, and reactive oxygen species (ROS) production of liver and skeletal muscle mitochondria isolated from ground squirrels (Ictidomys tridecemlineatus) during torpor and IBE to determine how mitochondrial metabolism is suppressed during torpor and how this suppression affects oxidative stress. In liver and skeletal muscle, state 3 respiration measured at 37°C with succinate was 70% and 30% lower, respectively, during torpor. In liver, this suppression was achieved largely via inhibition of substrate oxidation, likely at succinate dehydrogenase. In both tissues, respiration by torpid mitochondria further declined up to 88% when mitochondria were cooled to 10°C, close to torpid T b. In liver, this passive thermal effect on respiration rate reflected reduced activity of all components of oxidative phosphorylation (substrate oxidation, phosphorylation, and proton leak). With glutamate ϩ malate and succinate, mitochondrial free radical leak (FRL; proportion of electrons leading to ROS production) was higher in torpor than IBE, but only in liver. With succinate, higher FRL likely resulted from increased reduction state of complex III during torpor. With glutamate ϩ malate, higher FRL resulted from active suppression of complex I ROS production during IBE, which may limit ROS production during arousal. In both tissues, ROS production and FRL declined with temperature, suggesting ROS production is also reduced during torpor by passive thermal effects. hydrogen peroxide; top-down elasticity analysis; oxidative phosphorylation; oxidative stress HIBERNATION IN SMALL MAMMALS involves repeated bouts of torpor, during which metabolic rate (MR) and body temperature (T b ) decline to low levels [typically 5% of basal metabolic rate (BMR) and 5°C, respectively] for several days (31). Torpor bouts are spontaneously interrupted by periods of interbout euthermia, during which MR rapidly returns to typical resting levels, and T b returns to ϳ37°C for several hours (31). The suppression of MR during torpor is not simply a consequence of lowered T b but rather involves an active, regulated inhibition (38). Many studies have investigated whether active inhibition of mitochondrial respiration contributes to this MR suppression, since mitochondria are responsible for up to 90% of whole-animal oxygen consumption and have considerable control over cellular energy-demanding processes (63). Respiration rates of isolated mi...

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Thermoregulatory, carboxyatractylate‐sensitive uncoupling in heart and skeletal muscle mitochondria of the ground squirrel correlates with the level of free fatty acids

Cited by 30 publications

References 14 publications

Cyclosporin A suppression of uncoupling in liver mitochondria of ground squirrel during arousal from hibernation

Cyclosporin A suppression of uncoupling in liver mitochondria of ground squirrel during arousal from hibernation

Tissue-specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels

Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen-lined ground squirrels

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