Mitochondrial dynamics in astrocytes

Stephen, Terri‐Leigh; Gupta‐Agarwal, Swati; Kittler, Josef T.

doi:10.1042/bst20140195

Cited by 42 publications

(35 citation statements)

References 114 publications

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“…While GLT-1 (GLAST, glutamine synthetase, Na + /K + -ATPase, etc) have been localized to the fine processes of astrocytes (Chaudhry et al, 1995; Cholet et al, 2002; Norenberg and Martinez-Hernandez, 1979), there was a general belief that mitochondria were too large to fit into these fine processes (in many other cells mitochondria are 1 μm in diameter or larger). In fact, several studies have demonstrated the presence of mitochondria in fine astrocytic processes (Aoki et al, 1987; Derouiche et al, 2015; Fernandez et al, 1983; Genda et al, 2011; Jackson et al, 2014; Lovatt et al, 2007; Mathiisen et al, 2010; Motori et al, 2013; Mugnaini, 1964; Oberheim et al, 2009; Stephen et al, 2015; Xu et al, 2003 for review, see Stephen et al, 2014). In organotypic hippocampal slice cultures, mitochondria occupy 45% of the average astrocytic process and overlap with GLT-1 puncta occurs more often than would occur by chance (~70% of the time) (Genda et al, 2011).…”

Section: Coupling Of Glutamate Transport To Mitochondriamentioning

confidence: 99%

Astroglial glutamate transporters coordinate excitatory signaling and brain energetics

Robinson

Jackson

2016

Neurochemistry International

137

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In the mammalian brain, a family of sodium-dependent transporters maintains low extracellular glutamate and shapes excitatory signaling. The bulk of this activity is mediated by the astroglial glutamate transporters GLT-1 and GLAST (also called EAAT2 and EAAT1). In this review, we will discuss evidence that these transporters co-localize with, form physical (co-immunoprecipitable) interactions with, and functionally couple to various ‘energy-generating’ systems, including the Na+/K+-ATPase, the Na+/Ca2+ exchanger, glycogen metabolizing enzymes, glycolytic enzymes, and mitochondria/mitochondrial proteins. This functional coupling is bidirectional with many of these systems both being regulated by glutamate transport and providing the ‘fuel’ to support glutamate uptake. Given the importance of glutamate uptake to maintaining synaptic signaling and preventing excitotoxicity, it should not be surprising that some of these systems appear to ‘redundantly’ support the energetic costs of glutamate uptake. Although the glutamate-glutamine cycle contributes to recycling of neurotransmitter pools of glutamate, this is an over-simplification. The ramifications of co-compartmentalization of glutamate transporters with mitochondria for glutamate metabolism are discussed. Energy consumption in the brain accounts for ~20% of the basal metabolic rate and relies almost exclusively on glucose for the production of ATP. However, the brain does not possess substantial reserves of glucose or other fuels. To ensure adequate energetic supply, increases in neuronal activity are matched by increases in cerebral blood flow via a process known as ‘neurovascular coupling’. While the mechanisms for this coupling are not completely resolved, it is generally agreed that astrocytes, with processes that extend to synapses and endfeet that surround blood vessels, mediate at least some of the signal that causes vasodilation. Several studies have shown that either genetic deletion or pharmacologic inhibition of glutamate transport impairs neurovascular coupling. Together these studies strongly suggest that glutamate transport not only coordinates excitatory signaling, but also plays a pivotal role in regulating brain energetics.

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Section: Coupling Of Glutamate Transport To Mitochondriamentioning

confidence: 99%

Astroglial glutamate transporters coordinate excitatory signaling and brain energetics

Robinson

Jackson

2016

Neurochemistry International

137

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“…In particular, the GFAP-positive perinuclear cytoplasm and stem processes are known to be rich in mitochondria, whereas the PAPs would appear too narrow to contain mitochondria, and would thus not rely on oxidative metabolism. In particular, the GFAP-positive perinuclear cytoplasm and stem processes are known to be rich in mitochondria, whereas the PAPs are generally assumed too narrow to contain mitochondria, and to rely instead on glycolysis, glycogenolysis and ATP diffusion from the stem processes [3,28].…”

Section: Introductionmentioning

confidence: 99%

Fine Astrocyte Processes Contain Very Small Mitochondria: Glial Oxidative Capability May Fuel Transmitter Metabolism

2015

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The peripheral astrocyte process (PAP) is the glial compartment largely handling inactivation of transmitter glutamate, and supplying glutamate to the axon terminal. It is not clear how these energy demanding processes are fueled, and whether the PAP exhibits oxidative capability. Whereas the GFAP-positive perinuclear cytoplasm and stem process are rich in mitochondria, the PAP is often considered too narrow to contain mitochondria and might thus not rely on oxidative metabolism. Applying high resolution light microscopy, we investigate here the presence of mitochondria in the PAPs of freshly dissociated, isolated astrocytes. We provide an overview of the subcellular distribution and the approximate size of astrocytic mitochondria. A substantial proportion of the astrocyte's mitochondria are contained in the PAPs and, on the average, they are smaller there than in the stem processes. The majority of mitochondria in the stem and peripheral processes are surprisingly small (0.2-0.4 µm), spherical and not elongate, or tubular, which is supported by electron microscopy. The density of mitochondria is two to several times lower in the PAPs than in the stem processes. Thus, PAPs do not constitute a mitochondria free glial compartment but contain mitochondria in large numbers. No juxtaposition of mitochondria-containing PAPs and glutamatergic synapses has been reported. However, the issue of sufficient ATP concentrations in perisynaptic PAPs can be seen in the light of (1) the rapid, activity dependent PAP motility, and (2) the recently reported activity-dependent mitochondrial transport and immobilization leading to spatial, subcellular organisation of glutamate uptake and oxidative metabolism.

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“…For example, it is now known that astrocytes have a key role in the regulation and support of the neuronal mitochondrial quality control [79,80]. Furthermore, recent studies in the AD field have shifted attention from the "amyloid hypothesis" to the "neuroenergetic hypothesis" [81], thereby focusing on the importance of the cellular bioenergetic interplay in disease conditions.…”

Section: Impaired Mitochondrial Function In Alzheimer's Disease: Focumentioning

confidence: 99%

Mitochondrial Function in Alzheimer’s Disease: Focus on Astrocytes

Lampinen¹,

Belaya²,

Boccuni³

et al. 2018

Astrocyte - Physiology and Pathology

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The brain is one of the most energy-requiring organs in the human body. Mitochondria not only generate this energy, but are centrally involved critical cellular functions including maintenance of calcium homeostasis, synthesis of biomolecules, and cell signaling. Even though neurons and astrocytes preferentially use different energy substrates and metabolic pathways, these two cell types are intricately linked in their energy metabolism. Recently it has become clear that astrocytes have a key role in the regulation and support of the neuronal mitochondrial quality control, yet several questions remain unanswered to fully understand the mechanisms of mitochondrial function, transport, turnover and degradation in astrocytes. Alzheimer's disease is the most common neurodegenerative disorder, the exact mechanisms of which remain incompletely understood. The fact that astrocytic mitochondrial dysfunction is an early event in the pathogenesis of Alzheimer's disease suggests that more research on mitochondrial function and impairment is required in the hopes of disease alleviation in the future.

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Mitochondrial dynamics in astrocytes

Cited by 42 publications

References 114 publications

Astroglial glutamate transporters coordinate excitatory signaling and brain energetics

Astroglial glutamate transporters coordinate excitatory signaling and brain energetics

Fine Astrocyte Processes Contain Very Small Mitochondria: Glial Oxidative Capability May Fuel Transmitter Metabolism

Mitochondrial Function in Alzheimer’s Disease: Focus on Astrocytes

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