Drosophila alicorn Is a Neuronal Maintenance Factor Protecting against Activity-Induced Retinal Degeneration

Spasic, Milos; Callaerts, Patrick; Norga, Koenraad

doi:10.1523/jneurosci.1646-08.2008

Cited by 52 publications

(55 citation statements)

References 65 publications

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“…How AMPK␣2 increases neuronal damage is still unclear, but it has been speculated that it involves the regulation of neuronal NO, which appears to be detrimental to recovery following ischemia (321). AMPK has recently been shown to be important in preventing retinal degeneration in the Drosophila visual system using deletion of the ␤ subunit (458). Mutation of the Drosophila AMPK ␥ subunit also results in progressive neurodegeneration phenotype (442,503).…”

Section: E Dementia Neurogenesis and Strokementioning

confidence: 99%

AMPK in Health and Disease

Steinberg¹,

Kemp²

2009

Physiological Reviews

1,459

1,419

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The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ heterotrimer has emerged as an important integrator of signals that control energy balance through the regulation of multiple biochemical pathways in all eukaryotes. In this review, we begin with the discovery of the AMPK family and discuss the recent structural studies that have revealed the molecular basis for AMP binding to the enzyme's γ subunit. AMPK's regulation involves autoinhibitory features and phosphorylation of both the catalytic α subunit and the β-targeting subunit. We review the role of AMPK at the cellular level through examination of its many substrates and discuss how it controls cellular energy balance. We look at how AMPK integrates stress responses such as exercise as well as nutrient and hormonal signals to control food intake, energy expenditure, and substrate utilization at the whole body level. Lastly, we review the possible role of AMPK in multiple common diseases and the role of the new age of drugs targeting AMPK signaling.

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Section: E Dementia Neurogenesis and Strokementioning

confidence: 99%

AMPK in Health and Disease

Steinberg¹,

Kemp²

2009

Physiological Reviews

1,459

1,419

View full text Add to dashboard Cite

show abstract

“…The AMPKa homologs in C. elegans (AAK1 and AAK2) and D. melanogaster (SNF1A) are activated by AMP (Pan and Hardie 2002;Apfeld et al 2004). In D. melanogaster, AMPK is important for cellular homeostasis and survival on energy deprivation (Tschape et al 2002;Lee et al 2007;Spasic et al 2008). In A. thaliana, the Snf1 and AMPKa homologs are the sucrose nonfermenting-1-related protein kinase 1 (SnRK1) subfamily members, KIN10 and KIN11.…”

Section: Ampk Signalingmentioning

confidence: 99%

The Opposing Actions of Target of Rapamycin and AMP-Activated Protein Kinase in Cell Growth Control

Hindupur

González

Hall

2015

Cold Spring Harb Perspect Biol

121

107

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“…The ␥ subunits are nucleotide binding regulatory subunits that bind AMP. The conserved C terminus of the ␤ subunit interacts with both the ␣ and ␥ subunits and plays an obligatory role in AMPK complex formation (10,46). In addition, ␤ subunits contain a conserved carbohydrate-binding domain that allows AMPK to function as a glycogen sensor (37,42).…”

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confidence: 99%

The AMPK β2 Subunit Is Required for Energy Homeostasis during Metabolic Stress

Dasgupta

Sasaki

et al. 2012

Molecular and Cellular Biology

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AMP activated protein kinase (AMPK) plays a key role in the regulatory network responsible for maintaining systemic energy homeostasis during exercise or nutrient deprivation. To understand the function of the regulatory ␤2 subunit of AMPK in systemic energy metabolism, we characterized ␤2 subunit-deficient mice. Using these mutant mice, we demonstrated that the ␤2 subunit plays an important role in regulating glucose, glycogen, and lipid metabolism during metabolic stress. The ␤2 mutant animals failed to maintain euglycemia and muscle ATP levels during fasting. In addition, ␤2-deficient animals showed classic symptoms of metabolic syndrome, including hyperglycemia, glucose intolerance, and insulin resistance when maintained on a high-fat diet (HFD), and were unable to maintain muscle ATP levels during exercise. Cell surface-associated glucose transporter levels were reduced in skeletal muscle from ␤2 mutant animals on an HFD. In addition, they displayed poor exercise performance and impaired muscle glycogen metabolism. These mutant mice had decreased activation of AMPK and deficits in PGC1␣-mediated transcription in skeletal muscle. Our results highlight specific roles of AMPK complexes containing the ␤2 subunit and suggest the potential utility of AMPK isoform-specific pharmacological modulators for treatment of metabolic, cardiac, and neurological disorders. AMP activated protein kinase (AMPK) plays a crucial role in maintaining systemic energy homeostasis through its coordinated actions on the central nervous system and peripheral tissues (54). Loss of AMPK function causes metabolic abnormalities in mice and defects in development and growth, cell polarity, and structure in plants, Drosophila, and rodents (1, 10, 33). Moreover, AMPK is necessary for caloric restriction-mediated longevity in Caenorhabditis elegans (19). AMPK is an intracellular energy sensor. When intracellular levels of ATP decrease, a corresponding increase in AMP leads to activation of AMPK, a step that is vital for restoring intracellular energy balance via AMPK-dependent inhibition of energy-consuming biosynthetic processes and concomitant activation of pathways that increase ATP production.AMPK is a multisubstrate, heterotrimeric serine/threonine kinase consisting of one ␣, one ␤, and one ␥ subunit. The mammalian genome encodes two ␣, two ␤, and three ␥ subunits. The N terminus of the ␣ subunit contains the catalytic domain as well as a phosphorylation site for upstream kinases that regulate its activity (9). The ␥ subunits are nucleotide binding regulatory subunits that bind AMP. The conserved C terminus of the ␤ subunit interacts with both the ␣ and ␥ subunits and plays an obligatory role in AMPK complex formation (10, 46). In addition, ␤ subunits contain a conserved carbohydrate-binding domain that allows AMPK to function as a glycogen sensor (37,42).While AMPK is present in all tissues, the individual AMPK subunits display considerable variation in tissue-specific expression, subunit association, and subcellular localization. Earlie...

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Drosophila alicorn Is a Neuronal Maintenance Factor Protecting against Activity-Induced Retinal Degeneration

Cited by 52 publications

References 65 publications

AMPK in Health and Disease

AMPK in Health and Disease

The Opposing Actions of Target of Rapamycin and AMP-Activated Protein Kinase in Cell Growth Control

The AMPK β2 Subunit Is Required for Energy Homeostasis during Metabolic Stress

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