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Alexandros K Kanellopoulos et al.
Cell, 180(6), 1178-1197 (2020-03-24)
Social impairment is frequently associated with mitochondrial dysfunction and altered neurotransmission. Although mitochondrial function is crucial for brain homeostasis, it remains unknown whether mitochondrial disruption contributes to social behavioral deficits. Here, we show that Drosophila mutants in the homolog of
Aditi Sharma et al.
Science advances, 8(39), eabq5575-eabq5575 (2022-09-29)
The connections between metabolic state and therapy resistance in multiple myeloma (MM) are poorly understood. We previously reported that electron transport chain (ETC) suppression promotes sensitivity to the BCL-2 antagonist venetoclax. Here, we show that ETC suppression promotes resistance to
Dale Gottlieb et al.
Biological imaging, 3, e21-e21 (2024-03-15)
Fluorescence lifetime imaging microscopy (FLIM) is a powerful technique used to probe the local environment of fluorophores. The fit-free phasor approach to FLIM data is increasingly being used due to its ease of interpretation. To date, no open-source graphical user
Natalia Smith-Cortinez et al.
Cells, 9(11) (2020-11-15)
Upon liver injury, hepatic stellate cells (HSCs) transdifferentiate to migratory, proliferative and extracellular matrix-producing myofibroblasts (e.g., activated HSCs; aHSCs) causing liver fibrosis. HSC activation is associated with increased glycolysis and glutaminolysis. Here, we compared the contribution of glycolysis, glutaminolysis and
Hayato Hikita et al.
Cancer prevention research (Philadelphia, Pa.), 8(8), 693-701 (2015-06-04)
Chronic hepatitis, including viral hepatitis and steatihepatitis, is a well-known high-risk condition for hepatocellular carcinoma. We previously reported that continuous hepatocyte apoptosis drives liver tumors in hepatocyte-specific Bcl-xL or Mcl-1 knockout mice. In this study, we further examine the underlying
Lisa S Pike Winer et al.
PloS one, 9(10), e109916-e109916 (2014-11-02)
Cancer cells exhibit remarkable alterations in cellular metabolism, particularly in their nutrient substrate preference. We have devised several experimental methods that rapidly analyze the metabolic substrate flux in cancer cells: glycolysis and the oxidation of major fuel substrates glucose, glutamine
Tommy Weiss-Sadan et al.
Cell metabolism, 35(3), 487-503 (2023-02-26)
Multiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator, KEAP1. NRF2 has been studied extensively in KEAP1-mutant cancers; however, the role of this pathway in cancers with wild-type KEAP1 remains poorly understood.
Alba Sabaté-Pérez et al.
Autophagy, 19(3), 904-925 (2022-08-11)
Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that induces brown adipose
Remi Hatinguais et al.
Frontiers in immunology, 12, 641495-641495 (2021-04-13)
Reactive Oxygen Species (ROS) are highly reactive molecules that can induce oxidative stress. For instance, the oxidative burst of immune cells is well known for its ability to inhibit the growth of invading pathogens. However, ROS also mediate redox signalling
Luiz G B Michelini et al.
Neuroscience letters, 589, 25-30 (2015-01-18)
Chronic and systemic treatment of rodents with rotenone, a classical inhibitor of mitochondrial respiratory complex I, results in neurochemical, behavioral, and neuropathological features of Parkinson's disease. The aim of the present study was to evaluate whether brain mitochondria from old
Snehasis Biswas et al.
Journal of Ayurveda and integrative medicine, 15(1), 100854-100854 (2023-12-26)
Neurodegenerative diseases have been one of the major concerns for human health. Genetic and environmental factors are believed to be responsible for neuronal diseases such as Parkinson's disease, Alzheimer's disease, and Huntington's disease. It is difficult to restore normal nervous
Ling Jin et al.
BMB reports, 54(11), 563-568 (2021-09-08)
Cancer cells predominantly generate energy via glycolysis, even in the presence of oxygen, to support abnormal cell proliferation. Suppression of PDHA1 by PDK1 prevents the conversion of cytoplasmic pyruvate into Acetyl-CoA. Several PDK inhibitors have been identified, but their clinical
Alexander Duscha et al.
Cell, 180(6), 1067-1080 (2020-03-12)
Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly
Chris Donnelly et al.
Redox biology, 71, 103037-103037 (2024-02-25)
Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in
Anna-Karin Persson et al.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(49), 19250-19261 (2013-12-07)
Axonal degeneration occurs in multiple neurodegenerative disorders of the central and peripheral nervous system. Although the underlying molecular pathways leading to axonal degeneration are incompletely understood, accumulating evidence suggests contributions of impaired mitochondrial function, disrupted axonal transport, and/or dysfunctional intracellular
Rita Soares et al.
Life science alliance, 7(7) (2024-04-26)
Neural stem cells (NSCs) reside in discrete regions of the adult mammalian brain where they can differentiate into neurons, astrocytes, and oligodendrocytes. Several studies suggest that mitochondria have a major role in regulating NSC fate. Here, we evaluated mitochondrial properties
Camilla Soragni et al.
Redox biology, 57, 102488-102488 (2022-10-07)
Reactive oxygen species (ROS) have different properties and biological functions. They contribute to cell signaling and, in excessive amounts, to oxidative stress (OS). Although ROS is pivotal in a wide number of physiological systems and pathophysiological processes, direct quantification in
Andrew Y Sung et al.
Nature metabolism, 6(6), 1128-1142 (2024-05-09)
Isolated complex I (CI) deficiencies are a major cause of primary mitochondrial disease. A substantial proportion of CI deficiencies are believed to arise from defects in CI assembly factors (CIAFs) that are not part of the CI holoenzyme. The biochemistry
Sean Ekins et al.
Drug metabolism and disposition: the biological fate of chemicals, 38(12), 2302-2308 (2010-09-17)
Drug-induced liver injury (DILI) is one of the most important reasons for drug development failure at both preapproval and postapproval stages. There has been increased interest in developing predictive in vivo, in vitro, and in silico models to identify compounds
Hamidullah Khan et al.
Cell reports, 29(10), 3009-3018 (2019-12-05)
Metabolic flexibility allows cells to adapt to various environments and limits the efficacy of metabolic drugs. Therapeutic targeting of cancer metabolism relies on defining limiting requirements and vulnerabilities in the highly dynamic metabolic network. Here, we characterize the metabolic reprogramming
Francisco J Rios et al.
The Journal of pharmacology and experimental therapeutics, 353(1), 27-34 (2015-01-27)
Hyperaldosteronism and hypertension were unexpected side effects observed in trials of torcetrapib, a cholesteryl ester-transfer protein (CETP) inhibitor that increases high-density lipoprotein. Given that CETP inhibitors are lipid soluble, accumulate in adipose tissue, and have binding sites for proteins involved
Reinforcement Learning Recruits Somata and Apical Dendrites across Layers of Primary Sensory Cortex.
Clay O Lacefield et al.
Cell reports, 26(8), 2000-2008 (2019-02-21)
The mammalian brain can form associations between behaviorally relevant stimuli in an animal's environment. While such learning is thought to primarily involve high-order association cortex, even primary sensory areas receive long-range connections carrying information that could contribute to high-level representations.
Jaeyoung Ha et al.
Communications biology, 4(1), 1123-1123 (2021-09-25)
The highly cytotoxic marine natural product callyspongiolide holds great promise as a warhead of antibody-drug conjugate in cancer therapeutics; however, the mechanism underlying its cytotoxicity remains unclear. To elucidate how callyspongiolide kills cells, we employed label-free target identification with thermal
Daniel Alvarez-Fischer et al.
Journal of neurochemistry, 127(6), 782-792 (2013-06-28)
The uricosuric agent probenecid is co-administered with the dopaminergic neurotoxin MPTP to produce a chronic mouse model of Parkinson's disease. It has been proposed that probenecid serves to elevate concentrations of MPTP in the brain by reducing renal elimination of
Neal J Dawson et al.
eLife, 9 (2020-07-31)
High-altitude environments require that animals meet the metabolic O2 demands for locomotion and thermogenesis in O2-thin air, but the degree to which convergent metabolic changes have arisen across independent high-altitude lineages or the speed at which such changes arise is
Brandon Gaitan et al.
Metabolites, 12(11) (2022-11-25)
Breast cancer is the most diagnosed cancer type in women, with it being the second most deadly cancer in terms of total yearly mortality. Due to the prevalence of this disease, better methods are needed for both detection and treatment.
Yan Chen et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(5), 6688-6702 (2020-03-27)
Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize
Rawand Masoud et al.
Cell reports. Medicine, 1(8), 100143-100143 (2020-12-10)
Mitochondrial respiration (oxidative phosphorylation, OXPHOS) is an emerging target in currently refractory cancers such as pancreatic ductal adenocarcinoma (PDAC). However, the variability of energetic metabolic adaptations between PDAC patients has not been assessed in functional investigations. In this work, we
Haiyuan Zhang et al.
PloS one, 9(5), e96418-e96418 (2014-05-09)
Gambogic acid (GA), the main active component of gamboge resin, has potent antitumor activity both in vivo and in vitro. However, the underlying molecular mechanisms remain unclear. In this study, we found that GA could initiate autophagy in colorectal cancer
Judith M Hollander et al.
Communications biology, 5(1), 1230-1230 (2022-11-13)
Long bone growth requires the precise control of chondrocyte maturation from proliferation to hypertrophy during endochondral ossification, but the bioenergetic program that ensures normal cartilage development is still largely elusive. We show that chondrocytes have unique glucose metabolism signatures in
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