ATP from glycolysis is required for normal sodium homeostasis in resting fast-twitch rodent skeletal muscle

Okamoto, Ken; Wang, Weiyang; Rounds, J. A.N.; Chambers, Elizabeth A.; Jacobs, Danny O.

doi:10.1152/ajpendo.2001.281.3.e479

Cited by 64 publications

(60 citation statements)

References 42 publications

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“…Validation of this approach comes from a direct comparison of mitochondrial respiration under aerobic conditions vs. net ATP turnover during anoxia in isolated mouse muscles (27) and in vivo in rattlesnake tailshaker muscle (28). Anoxia of up to 30 min in intact muscle does not impact the activity of a key ATPase in resting muscle, Na-K-ATPase (29), and our measurements of glycolysis indicate a negligible contribution to ATP supply during the anoxic period (Ͻ8%). Thus, brief anoxia appears to not affect cell ATP use nor raise glycolysis, which allows us to use the ATP turnover as a measure of the mitochondrial ATP generation under aerobic conditions.…”

Section: Discussionmentioning

confidence: 83%

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Amara¹,

Shankland²,

Jubrias³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

202

195

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Faster aging is predicted in more active tissues and animals because of greater reactive oxygen species generation. Yet age-related cell loss is greater in less active cell types, such as type II muscle fibers. Mitochondrial uncoupling has been proposed as a mechanism that reduces reactive oxygen species production and could account for this paradox between longevity and activity. We distinguished these hypotheses by using innovative optical and magnetic resonance spectroscopic methods applied to noninvasively measured ATP synthesis and O 2 uptake in vivo in human muscle. Here we show that mitochondrial function is unchanged with age in mildly uncoupled tibialis anterior muscle (75% type I) despite a high respiratory rate in adults. In contrast, substantial uncoupling and loss of cellular [ATP] indicative of mitochondrial dysfunction with age was found in the lower respiring and well coupled first dorsal interosseus (43-50% type II) of the same subjects. These results reject respiration rate as the sole factor impacting the tempo of cellular aging. Instead, they support mild uncoupling as a mechanism protecting mitochondrial function and contributing to the paradoxical longevity of the most active muscle fibers. magnetic resonance spectroscopy ͉ optical spectroscopy ͉ oxidative phosphorylation T he rate-of-living hypothesis proposes that higher rates of oxidative metabolism cause an increased production of reactive oxygen species (ROS) (1), leading to oxidative damage and mitochondrial dysfunction with age. However, mice with the lowest resting respiration rate have been shown to have the shortest longevity (2). Similarly, isolated muscle fibers show greater generation of ROS in type II fibers (3), which have the lowest oxidative capacity and chronic activity levels. This fiber type also has the shortest longevity and is the first to be lost with age (4). Thus, the tempo of aging appears to vary among mice and muscle fiber types but in an opposite manner than predicted by the rate-of-living hypothesis, with the least active having the shortest longevity.A physiological mechanism that could account for this paradox is mild mitochondrial uncoupling, which has been proposed to ameliorate ROS production by reducing reverse electron flow and superoxide generation (5). Consistent with this prediction are findings in mice with high respiration rates that showed elevated proton leak in isolated muscle mitochondria as a result of activation of the adenine nucleotide translocator and uncoupling protein 3. Mild uncoupling resulting from activation of these mitochondrial factors in type I muscle fibers could reduce ROS production, protect mitochondria from damage, and account for the longevity of this fiber type with age. A number of studies have provided evidence of mild uncoupling in human muscles (6, 7) but have not tested whether this uncoupling protects against mitochondrial dysfunction and cellular aging.New methods permit measurement of mitochondrial coupling in vivo by using a combination of noninvasive spectroscopi...

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Section: Discussionmentioning

confidence: 83%

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Amara¹,

Shankland²,

Jubrias³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

202

195

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“…This ionic pump is fueled at least partially by glycolytic ATP in both neurons and glial cells (Silver et al, 1997). A functional association at the membrane between GAPDH and (Na ϩ ,K ϩ )-ATPase and a preference for glycolytic ATP were clearly demonstrated in erythrocytes, in cardiac Purkinje cells, and in fast-twitch skeletal muscle (Mercer and Dunham, 1981;Glitsch and Tappe, 1993;Okamoto et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Glyceraldehyde-3-Phosphate Dehydrogenase Is a GABA_AReceptor Kinase Linking Glycolysis to Neuronal Inhibition

Khallou-Laschet¹,

Minier²,

Kurcewicz³

et al. 2004

J. Neurosci.

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Protein phosphorylation is crucial for regulating synaptic transmission. We describe a novel mechanism for the phosphorylation of the GABA A receptor, which mediates fast inhibition in the brain. A protein copurified and coimmunoprecipitated with the phosphorylated receptor ␣1 subunit; this receptor-associated protein was identified by purification and microsequencing as the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Molecular constructs demonstrated that GAPDH directly phosphorylates the long intracellular loop of GABA A receptor ␣1 subunit at identified serine and threonine residues. GAPDH and the ␣1 subunit were found to be colocalized at the neuronal plasma membrane. In keeping with the GAPDH/GABA A receptor molecular association, glycolytic ATP produced locally at plasma membranes was consumed for this ␣1 subunit phosphorylation, possibly within a single macrocomplex. The membrane-attached GAPDH is thus a dual-purpose enzyme, a glycolytic dehydrogenase, and a receptor-associated kinase. In acutely dissociated cortical neurons, the rundown of the GABA A responses was essentially attributable to a Mg 2ϩ -dependent phosphatase activity, which was sensitive to vanadate but insensitive to okadaic acid or fluoride. Rundown was significantly reduced by the addition of GAPDH or its reduced cofactor NADH and nearly abolished by the addition of its substrate glyceraldehyde-3-phosphate (G3P). The prevention of rundown by G3P was abolished by iodoacetamide, an inhibitor of the dehydrogenase activity of GAPDH, indicating that the GABA A responses are maintained by a glycolysis-dependent phosphorylation. Our results provide a molecular mechanism for the direct involvement of glycolysis in neurotransmission.

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“…Glutamate is cleared from the synapse by a sodium-coupled process. Sodium then must be removed from the astrocytes by Na/K-ATPase, a pump fueled by glycolysis in all cell systems in which it is found (41)(42)(43)(44)(45), probably because it delivers ATP at twice the rate of oxidative phosphorylation (46). Failure to remove glutamate efficiently from the synapse can be damaging because excessive glutamate acts as an excitatory neurotoxin (47,48).…”

Section: Discussionmentioning

confidence: 99%

Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition

Vlassenko¹,

Vaishnavi²,

Couture³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

352

303

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Amyloid-β (Aβ) plaque deposition can precede the clinical manifestations of dementia of the Alzheimer type (DAT) by many years and can be associated with changes in brain metabolism. Both the Aβ plaque deposition and the changes in metabolism appear to be concentrated in the brain's default-mode network. In contrast to prior studies of brain metabolism which viewed brain metabolism from a unitary perspective that equated glucose utilization with oxygen consumption, we here report on regional glucose use apart from that entering oxidative phosphorylation (so-called "aerobic glycolysis"). Using PET, we found that the spatial distribution of aerobic glycolysis in normal young adults correlates spatially with Aβ deposition in individuals with DAT and cognitively normal participants with elevated Aβ, suggesting a possible link between regional aerobic glycolysis in young adulthood and later development of Alzheimer pathology.Alzheimer's disease | default mode network | positron emission tomography C erebral amyloid-β (Aβ) plaque deposition is a hallmark of Alzheimer's disease (AD) (1, 2), and there is clinical pathological evidence that Aβ deposition may precede clinical manifestation of cognitive deficits and dementia of the Alzheimer type (DAT) (3, 4). However, it is unclear whether the site and extent of Aβ deposition is related to any preceding pattern of brain activity or metabolism.A radiotracer with high affinity to Aβ plaques, N-methyl-[ 11 C] 2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (or 11 C-PIB, for "Pittsburgh Compound-B"), has been developed for PET study and has demonstrated substantially increased regional uptake in individuals with DAT and also in some cognitively normal older persons (5-7). The spatial distribution of Aβ plaques by PET imaging in individuals with DAT appears strikingly similar to the default mode network (DMN), a group of brain regions that are more active when normal individuals are not engaged in attentiondemanding, goal-directed task performance (8-10).The unique distribution of Aβ in DAT suggests that something unique to these brain areas predisposes them to the pathophysiology of AD (9, 11). One of the many features of these areas is their reliance on glucose outside its usual role as substrate for oxidative phosphorylation (12). In adequately oxygenated tissue, this use of glucose usually is referred to as "aerobic glycolysis" and accounts for 10-15% of the glucose metabolized by the brain (13-15). It should be noted that the term "aerobic glycolysis" includes glycolysis itself (metabolism of glucose-6-phosphate to pyruvate) as well as glucose entering the pentose phosphate shunt and glycogen synthesis.Because many critical functions are associated with glucose outside its traditional role in supplying energy through oxidative phosphorylation (16)(17)(18)(19), this relationship might signal a causal element in the chain of events leading to DAT. As a first step in exploring this possibility, we wanted to confirm the apparent spatial relationship between DAT and those brai...

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ATP from glycolysis is required for normal sodium homeostasis in resting fast-twitch rodent skeletal muscle

Cited by 64 publications

References 42 publications

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Glyceraldehyde-3-Phosphate Dehydrogenase Is a GABA_AReceptor Kinase Linking Glycolysis to Neuronal Inhibition

Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition

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ATP from glycolysis is required for normal sodium homeostasis in resting fast-twitch rodent skeletal muscle

Cited by 64 publications

References 42 publications

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo

Glyceraldehyde-3-Phosphate Dehydrogenase Is a GABAAReceptor Kinase Linking Glycolysis to Neuronal Inhibition

Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ) deposition

Contact Info

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Glyceraldehyde-3-Phosphate Dehydrogenase Is a GABA_AReceptor Kinase Linking Glycolysis to Neuronal Inhibition