Fundamentals of cancer metabolism

Science Advances, Journal Year: 2016, Volume and Issue: 2(5)

Published: May 6, 2016

Researchers provide a conceptual framework to understand current knowledge of the fundamentals cancer metabolism.

Language: Английский

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Mitochondrial TCA cycle metabolites control physiology and disease

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 3, 2020

Abstract Mitochondria are signaling organelles that regulate a wide variety of cellular functions and can dictate cell fate. Multiple mechanisms contribute to communicate mitochondrial fitness the rest cell. Recent evidence confers new role for TCA cycle intermediates, generally thought be important biosynthetic purposes, as molecules with controlling chromatin modifications, DNA methylation, hypoxic response, immunity. This review summarizes by which abundance different metabolites controls function fate in contexts. We will focus on how these mediated affect physiology disease.

Language: Английский

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Reactive Oxygen Species in Metabolic and Inflammatory Signaling

Circulation Research, Journal Year: 2018, Volume and Issue: 122(6), P. 877 - 902

Published: March 15, 2018

Reactive oxygen species (ROS) are well known for their role in mediating both physiological and pathophysiological signal transduction. Enzymes subcellular compartments that typically produce ROS associated with metabolic regulation, diseases dysfunction may be influenced by changes redox balance. In this review, we summarize the current literature surrounding inflammatory focusing on transduction its relationship to disease progression. particular, examine production such as cytoplasm, mitochondria, peroxisome, endoplasmic reticulum discuss how influence processes proteasome function, autophagy, general signaling. We also highlight of regulation metabolic/inflammatory including atherosclerosis, diabetes mellitus, stroke. order develop therapies target oxidative signaling, it is vital understand balance signaling plays physiology pathophysiology, manipulation identity cellular tissue homeostasis. An increased understanding specific sources an appreciation metabolism help guide us effort treat cardiovascular diseases.

Language: Английский

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Mitochondrial membrane potential

Analytical Biochemistry, Journal Year: 2017, Volume and Issue: 552, P. 50 - 59

Published: July 12, 2017

Language: Английский

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Selective neuronal vulnerability in Parkinson disease

Nature reviews. Neuroscience, Journal Year: 2017, Volume and Issue: 18(2), P. 101 - 113

Published: Jan. 20, 2017

Language: Английский

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Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals

The Journal of Cell Biology, Journal Year: 2017, Volume and Issue: 216(7), P. 2027 - 2045

Published: May 31, 2017

Mitochondrial stress activates a mitonuclear response to safeguard and repair mitochondrial function adapt cellular metabolism stress. Using multiomics approach in mammalian cells treated with four types of stressors, we identify activating transcription factor 4 (ATF4) as the main regulator response. Surprisingly, canonical unfolded protein genes mediated by ATF5 are not activated. Instead, ATF4 expression cytoprotective genes, which reprogram through activation integrated (ISR). promotes local proteostatic reducing ribosomal proteins, inhibiting translation, coupling ISR attenuation function. Through trans–expression quantitative trait locus analysis, provide genetic evidence supporting role for Fh1 control Atf4 mammals. gene data from mice humans diseases, show that pathway is activated vivo upon Our illustrate value characterize complex networks versatile resource new regulators mitochondrial-related diseases.

Language: Английский

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Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer

Proceedings of the National Academy of Sciences, Journal Year: 2017, Volume and Issue: 114(43)

Published: Oct. 11, 2017

Significance Increasing evidence suggests that extracellular vesicles (EVs) can transfer genetic material to recipient cells. However, the mechanism and role of this phenomenon are largely unknown. Here we have made a remarkable discovery: EVs harbor full mitochondrial genome. These in turn their mtDNA cells with impaired metabolism, leading restoration metabolic activity. We determined hormonal therapy induces oxidative phosphorylation-deficient breast cancer cells, which be rescued via mtDNA-laden vesicles. Horizontal occurred stem-like was associated increased self-renewal potential these resistance therapy. propose occurs human EVs.

Language: Английский

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HIF1α and metabolic reprogramming in inflammation

Journal of Clinical Investigation, Journal Year: 2016, Volume and Issue: 126(10), P. 3699 - 3707

Published: Aug. 28, 2016

HIF1α is a common component of pathways involved in the control cellular metabolism and has role regulating immune cell effector functions. Additionally, critical for maturation dendritic cells activation T cells. induced LPS-activated macrophages, where it critically glycolysis induction proinflammatory genes, notably Il1b. The mechanism LPS-stimulated involves succinate, which inhibits prolyl hydroxylases (PHDs). Pyruvate kinase M2 (PKM2) also interacts with promotes function HIF1α. In another inflammatory type, Th17 cells, acts via retinoic acid-related orphan receptor-γt (RORγt) to drive differentiation. therefore key reprogrammer that gene expression.

Language: Английский

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AMPK Maintains Cellular Metabolic Homeostasis through Regulation of Mitochondrial Reactive Oxygen Species

Cell Reports, Journal Year: 2017, Volume and Issue: 21(1), P. 1 - 9

Published: Oct. 1, 2017

Reactive oxygen species (ROS) are continuously produced as a by-product of mitochondrial metabolism and eliminated via antioxidant systems. Regulation mitochondrially ROS is required for proper cellular function, adaptation to metabolic stress, bypassing senescence. Here, we report non-canonical regulation the energy sensor AMP-activated protein kinase (AMPK) by (mROS) that functions maintain homeostasis. We demonstrate physiological activator AMPK activation triggers PGC-1α-dependent response limits production. Cells lacking activity display increased levels undergo premature Finally, show AMPK-PGC-1α-dependent control regulates HIF-1α stabilization promote Warburg effect in cells signaling. These data highlight key function sensing resolving stress resistance maintaining balance.

Language: Английский

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ElemCor: accurate data analysis and enrichment calculation for high-resolution LC-MS stable isotope labeling experiments

BMC Bioinformatics, Journal Year: 2019, Volume and Issue: 20(1)

Published: Feb. 19, 2019

The investigation of intracellular metabolism is the mainstay in biotechnology and physiology settings. Intracellular metabolic rates are commonly evaluated using labeling pattern identified metabolites obtained from stable isotope experiments. or mass distribution vector describes fractional abundances all isotopologs with different masses as a result isotopic labeling, which typically resolved spectrometry. Because naturally occurring isotopes impurity also contribute to measured signals, patterns must be corrected obtain patterns. Since contaminant same nominal can modern spectrometers high resolution, correction process should resolution dependent.Here we present software tool, ElemCor, perform such data resolution-dependent manner. tool based on difference theory (MDT) information unlabeled samples (ULS) account for effects. MDT mathematical only requires chemical formulae correction. ULS semi-empirical additional measurement samples. We validate both methods show their improvement accuracy comprehensiveness over existing simulated experimental Saccharomyces cerevisiae. available at https://github.com/4dsoftware/elemcor .We two methods, ULS, correct LC-MS experiments natural abundance impurity. recommend low-mass compounds cost efficiency experiments, high-mass relatively large spectral inaccuracy that tracked by standards.

Language: Английский

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