Advertisement

Topics

Loss of a Negative Regulator of mTORC1 Induces Aerobic Glycolysis and Altered Fiber Composition in Skeletal Muscle.

08:00 EDT 15th May 2018 | BioPortfolio

Summary of "Loss of a Negative Regulator of mTORC1 Induces Aerobic Glycolysis and Altered Fiber Composition in Skeletal Muscle."

The conserved GATOR1 complex consisting of NPRL2-NPRL3-DEPDC5 inhibits mammalian target of rapamycin complex 1 (mTORC1) in response to amino acid insufficiency. Here, we show that loss of NPRL2 and GATOR1 function in skeletal muscle causes constitutive activation of mTORC1 signaling in the fed and fasted states. Muscle fibers of NPRL2 knockout animals are significantly larger and show altered fiber-type composition, with more fast-twitch glycolytic and fewer slow-twitch oxidative fibers. NPRL2 muscle knockout mice also have altered running behavior and enhanced glucose tolerance. Furthermore, loss of NPRL2 induces aerobic glycolysis and suppresses glucose entry into the TCA cycle. Such chronic activation of mTORC1 leads to compensatory increases in anaplerotic pathways to replenish TCA intermediates that are consumed for biosynthetic purposes. These phenotypes reveal a fundamental role for the GATOR1 complex in the homeostatic regulation of mitochondrial functions (biosynthesis versus ATP) to mediate carbohydrate utilization in muscle.

Affiliation

Journal Details

This article was published in the following journal.

Name: Cell reports
ISSN: 2211-1247
Pages: 1907-1914

Links

DeepDyve research library

PubMed Articles [15747 Associated PubMed Articles listed on BioPortfolio]

Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions.

To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mi...

Aerobic glycolysis in amyotrophic lateral sclerosis and Huntington's disease.

Neurodegenerative cells are the sites of numerous metabolic and energetic abnormalities with abnormalities in energy production. Energy is the primary determinant of neuronal viability. In neurodegene...

Tumor suppressor NPRL2 induces ROS production and DNA damage response.

The SEA/GATOR complex is an essential regulator of the mTORC1 pathway. In mammals the GATOR1 complex is composed of the proteins DEPDC5, NPRL2 and NPRL3. GATOR1 serves as an mTORC1 inhibitor and activ...

Positive and Negative Regulation of the Master Metabolic Regulator mTORC1 by Two Families of Legionella pneumophila Effectors.

All pathogens must acquire nutrients from their hosts. The intracellular bacterial pathogen Legionella pneumophila, the etiological agent of Legionnaires' disease, requires host amino acids for growth...

Fructose and glucose regulate mammalian target of rapamycin complex 1 and can activate lipogenic gene expression via distinct pathways.

Though calorically equivalent to glucose, fructose appears to be more lipogenic, leading to dyslipidemia, fatty liver disease, cardiovascular disease, and diabetes. To better understand how fructose i...

Clinical Trials [5365 Associated Clinical Trials listed on BioPortfolio]

Relationship Between BMI & HRR After 4 Weeks of Aerobic Training

World Health Organization (WHO) defined body mass index (BMI) as the ratio of weight in kilograms to the square of the height in meters (kg/m2). BMI has been used widely to diagnose obesit...

Investigating Fitness Interventions in the Elderly (INFINITE)

Aging is associated with declines in aerobic capacity, exercise tolerance, and functional endurance that lead to physical disability and loss of independence. Furthermore, the existing hi...

Hepcidin in Anemic Chronic Heart Failure (CHF) Patients

Background: Anemia in chronic heart failure (CHF) is directly linked to increased mortality and reduced exercise capacity. The pathomechanism for the development of anemia in CHF is not ...

Exercise Intolerance in Elderly Patients With HFpEF(Heart Failure With Preserved Ejection Fraction)

The purpose of this study is to examine the effects of weight loss via hypocaloric diet (CR)and aerobic exercise (AT) compared to the effects of weight loss via hypocaloric diet (CR), aero...

Lysosomal Movement and Anabolic Resistance

Age-associated loss of muscle mass, termed sarcopenia, is strongly associated with functional impairment and physical disability in the elderly. Maintenance or growth of muscle mass is mai...

Medical and Biotech [MESH] Definitions

A serine/threonine-protein kinase that functions in AUTOPHAGY in response to starvation. It acts on the PHOSPHATIDYLINOSITOL 3-KINASE complex PIK3C3 to regulate AUTOPHAGOSOME formation. It also functions as both a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) and is activated by AMPK, which it also negatively regulates.

A large group of aerobic bacteria which show up as pink (negative) when treated by the gram-staining method. This is because the cell walls of gram-negative bacteria are low in peptidoglycan and thus have low affinity for violet stain and high affinity for the pink dye safranine.

A group of gram-negative bacteria consisting of rod- and coccus-shaped cells. They are both aerobic (able to grow under an air atmosphere) and microaerophilic (grow better in low concentrations of oxygen) under nitrogen-fixing conditions but, when supplied with a source of fixed nitrogen, they grow as aerobes.

A genus of gram-negative, aerobic or microaerophilic, colorless filaments. It is nonfruiting, motile by gliding, and found in freshwater sediments and cow dung. One species (V. stercoraria) is considered morphologically to be a streptobacillus. That species is strictly aerobic and produces a homodimeric bacterial hemoglobin, especially under oxygen-limited growth conditions. (From Bergey's Manual of Determinative Bacteriology, 9th ed)

A transcriptional regulator in prokaryotes which, when activated by binding cyclic AMP, acts at several promoters. Cyclic AMP receptor protein was originally identified as a catabolite gene activator protein. It was subsequently shown to regulate several functions unrelated to catabolism, and to be both a negative and a positive regulator of transcription. Cell surface cyclic AMP receptors are not included (CYCLIC AMP RECEPTORS), nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins, which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Rheumatology
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...


Searches Linking to this Article