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Mediators of Inflammation 2017The progressive and fatal loss of upper (brain) and lower (spinal cord) motor neurons and muscle denervation concisely condenses the clinical picture of amyotrophic... (Review)
Review
The progressive and fatal loss of upper (brain) and lower (spinal cord) motor neurons and muscle denervation concisely condenses the clinical picture of amyotrophic lateral sclerosis (ALS). Despite the multiple mechanisms believed to underlie the selective loss of motor neurons, ALS aetiology remains elusive and obscure. Likewise, there is also a cluster of alterations in ALS patients in which muscle wasting, body weight loss, eating dysfunction, and abnormal energy dissipation coexist. Defective energy metabolism characterizes the ALS progression, and such paradox of energy balance stands as a challenge for the understanding of ALS pathogenesis. The hypermetabolism in ALS will be examined from tissue-specific energy imbalance (e.g., skeletal muscle) to major energetic pathways (e.g., AMP-activated protein kinase) and whole-body energy alterations including glucose and lipid metabolism, nutrition, and potential involvement of interorgan communication. From the point of view here expressed, the hypermetabolism in ALS should be evaluated as a magnifying glass through which looking at the ALS pathogenesis is from a different perspective in which defective metabolism can disclose novel mechanistic interpretations and lines of intervention.
Topics: Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Energy Metabolism; Humans
PubMed: 29081604
DOI: 10.1155/2017/7821672 -
Cell Metabolism May 2005The increasing prevalence of obesity and other nutrition-related chronic diseases has prompted considerable efforts to understand their pathogenesis and treatment. One... (Review)
Review
The increasing prevalence of obesity and other nutrition-related chronic diseases has prompted considerable efforts to understand their pathogenesis and treatment. One experimental approach is to overexpress, inactivate, or manipulate specific genes that regulate energy metabolism and fat storage. Many such techniques are fully established, routine tools in Drosophila and C. elegans, which provide elegant models for dissecting endocrine problems and metabolic pathways.
Topics: Animals; Caenorhabditis elegans; Drosophila melanogaster; Energy Metabolism; Fats; Humans; Lipase; Obesity; Recombinant Proteins
PubMed: 16054074
DOI: 10.1016/j.cmet.2005.04.008 -
International Journal of Molecular... Dec 2022Despite the remarkable progress in cancer treatment up to now, we are still far from conquering the disease. The most substantial change after the malignant... (Review)
Review
Despite the remarkable progress in cancer treatment up to now, we are still far from conquering the disease. The most substantial change after the malignant transformation of normal cells into cancer cells is the alteration in their metabolism. Cancer cells reprogram their metabolism to support the elevated energy demand as well as the acquisition and maintenance of their malignancy, even in nutrient-poor environments. The metabolic alterations, even under aerobic conditions, such as the upregulation of the glucose uptake and glycolysis (the Warburg effect), increase the ROS (reactive oxygen species) and glutamine dependence, which are the prominent features of cancer metabolism. Among these metabolic alterations, high glutamine dependency has attracted serious attention in the cancer research community. In addition, the oncogenic signaling pathways of the well-known important genetic mutations play important regulatory roles, either directly or indirectly, in the central carbon metabolism. The identification of the convergent metabolic phenotypes is crucial to the targeting of cancer cells. In this review, we investigate the relationship between cancer metabolism and the signal transduction pathways, and we highlight the recent developments in anti-cancer therapy that target metabolism.
Topics: Humans; Glutamine; Glycolysis; Neoplasms; Energy Metabolism; Signal Transduction; Glucose
PubMed: 36613455
DOI: 10.3390/ijms24010012 -
International Journal of Biological... 2011Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including... (Review)
Review
Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes.
Topics: Aging; Animals; Energy Metabolism; Mammals; Signal Transduction; Sirtuins
PubMed: 21614150
DOI: 10.7150/ijbs.7.575 -
American Journal of Physiology.... Oct 2020Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by short open-reading frames (sORF) in mitochondrial DNA that do not necessarily have... (Review)
Review
Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by short open-reading frames (sORF) in mitochondrial DNA that do not necessarily have traditional hallmarks of protein-coding genes. To date, eight MDPs have been identified, all of which have been shown to have various cyto- or metaboloprotective properties. The 12S ribosomal RNA () gene harbors the sequence for MOTS-c, whereas the other seven MDPs [humanin and small humanin-like peptides (SHLP) 1-6] are encoded by the 16S ribosomal RNA gene. Here, we review the evidence that endogenous MDPs are sensitive to changes in metabolism, showing that metabolic conditions like obesity, diabetes, and aging are associated with lower circulating MDPs, whereas in humans muscle MDP expression is upregulated in response to stress that perturbs the mitochondria like exercise, some mtDNA mutation-associated diseases, and healthy aging, which potentially suggests a tissue-specific response aimed at restoring cellular or mitochondrial homeostasis. Consistent with this, treatment of rodents with humanin, MOTS-c, and SHLP2 can enhance insulin sensitivity and offer protection against a range of age-associated metabolic disorders. Furthermore, assessing how mtDNA variants alter the functions of MDPs is beginning to provide evidence that MDPs are metabolic signal transducers in humans. Taken together, MDPs appear to form an important aspect of a retrograde signaling network that communicates mitochondrial status with the wider cell and to distal tissues to modulate adaptative responses to metabolic stress. It remains to be fully determined whether the metaboloprotective properties of MDPs can be harnessed into therapies for metabolic disease.
Topics: Animals; Energy Metabolism; Humans; Mitochondria; Mitochondrial Proteins; Peptides
PubMed: 32776825
DOI: 10.1152/ajpendo.00249.2020 -
Philosophical Transactions of the Royal... Jul 2013Life is the harnessing of chemical energy in such a way that the energy-harnessing device makes a copy of itself. This paper outlines an energetically feasible path from... (Review)
Review
Life is the harnessing of chemical energy in such a way that the energy-harnessing device makes a copy of itself. This paper outlines an energetically feasible path from a particular inorganic setting for the origin of life to the first free-living cells. The sources of energy available to early organic synthesis, early evolving systems and early cells stand in the foreground, as do the possible mechanisms of their conversion into harnessable chemical energy for synthetic reactions. With regard to the possible temporal sequence of events, we focus on: (i) alkaline hydrothermal vents as the far-from-equilibrium setting, (ii) the Wood-Ljungdahl (acetyl-CoA) pathway as the route that could have underpinned carbon assimilation for these processes, (iii) biochemical divergence, within the naturally formed inorganic compartments at a hydrothermal mound, of geochemically confined replicating entities with a complexity below that of free-living prokaryotes, and (iv) acetogenesis and methanogenesis as the ancestral forms of carbon and energy metabolism in the first free-living ancestors of the eubacteria and archaebacteria, respectively. In terms of the main evolutionary transitions in early bioenergetic evolution, we focus on: (i) thioester-dependent substrate-level phosphorylations, (ii) harnessing of naturally existing proton gradients at the vent-ocean interface via the ATP synthase, (iii) harnessing of Na(+) gradients generated by H(+)/Na(+) antiporters, (iv) flavin-based bifurcation-dependent gradient generation, and finally (v) quinone-based (and Q-cycle-dependent) proton gradient generation. Of those five transitions, the first four are posited to have taken place at the vent. Ultimately, all of these bioenergetic processes depend, even today, upon CO2 reduction with low-potential ferredoxin (Fd), generated either chemosynthetically or photosynthetically, suggesting a reaction of the type 'reduced iron → reduced carbon' at the beginning of bioenergetic evolution.
Topics: Acetyl Coenzyme A; Biological Evolution; Energy Metabolism; Gene Expression Regulation; Hydrothermal Vents
PubMed: 23754820
DOI: 10.1098/rstb.2013.0088 -
Ageing Research Reviews Mar 2015
Topics: Adaptation, Physiological; Aging; Brain; Energy Metabolism; Environment; Humans
PubMed: 25728594
DOI: 10.1016/j.arr.2015.02.002 -
Annals of the New York Academy of... Apr 2014The thyroid hormone (TH) plays a significant role in diverse processes related to growth, development, differentiation, and metabolism. TH signaling modulates energy... (Review)
Review
The thyroid hormone (TH) plays a significant role in diverse processes related to growth, development, differentiation, and metabolism. TH signaling modulates energy expenditure through both central and peripheral pathways. At the cellular level, the TH exerts its effects after concerted mechanisms facilitate binding to the TH receptor. In the hypothalamus, signals from a range of metabolic pathways, including appetite, temperature, afferent stimuli via the autonomic nervous system, availability of energy substrates, hormones, and other biologically active molecules, converge to maintain plasma TH at the appropriate level to preserve energy homeostasis. At the tissue level, TH actions on metabolism are controlled by transmembrane transporters, deiodinases, and TH receptors. In the modern environment, humans are susceptible to an energy surplus, which has resulted in an obesity epidemic and, thus, understanding the contribution of the TH to cellular and organism metabolism is increasingly relevant.
Topics: Animals; Basal Metabolism; Energy Metabolism; Homeostasis; Humans; Hypothalamus; Obesity; Receptors, Thyroid Hormone; Thyroid Hormones
PubMed: 24697152
DOI: 10.1111/nyas.12374 -
Current Opinion in Pharmacology Dec 2022Metabolism consists of life-sustaining chemical reactions involving metabolites. Historically, metabolites were defined as the intermediates or end products of... (Review)
Review
Metabolism consists of life-sustaining chemical reactions involving metabolites. Historically, metabolites were defined as the intermediates or end products of metabolism and considered to be passive participants changed by metabolic processes. However, recent research has redefined how we view metabolism. There is emerging evidence of metabolites which function to mediate cellular signalling and interorgan crosstalk, regulating local metabolism and systemic physiology. These bioactive metabolite signals have been termed metabokines. Metabokines regulate diverse energy metabolism pathways across multiple tissues, including fatty acid β-oxidation, mitochondrial oxidative phosphorylation, lipolysis, glycolysis and gluconeogenesis. There is increasing impetus to uncover novel metabokine signalling axes to better understand how these may be perturbed in metabolic diseases and determine their utility as therapeutic targets.
Topics: Humans; Energy Metabolism; Glycolysis; Lipolysis; Mitochondria
PubMed: 36137304
DOI: 10.1016/j.coph.2022.102286 -
Frontiers in Endocrinology 2020As important metabolic substrates, branched-chain amino acids (BCAAs) and fatty acids (FAs) participate in many significant physiological processes, such as... (Review)
Review
As important metabolic substrates, branched-chain amino acids (BCAAs) and fatty acids (FAs) participate in many significant physiological processes, such as mitochondrial biogenesis, energy metabolism, and inflammation, along with intermediate metabolites generated in their catabolism. The increased levels of BCAAs and fatty acids can lead to mitochondrial dysfunction by altering mitochondrial biogenesis and adenosine triphosphate (ATP) production and interfering with glycolysis, fatty acid oxidation, the tricarboxylic acid cycle (TCA) cycle, and oxidative phosphorylation. BCAAs can directly activate the mammalian target of rapamycin (mTOR) signaling pathway to induce insulin resistance, or function together with fatty acids. In addition, elevated levels of BCAAs and fatty acids can activate the canonical nuclear factor-κB (NF-κB) signaling pathway and inflammasome and regulate mitochondrial dysfunction and metabolic disorders through upregulated inflammatory signals. This review provides a comprehensive summary of the mechanisms through which BCAAs and fatty acids modulate energy metabolism, insulin sensitivity, and inflammation synergistically.
Topics: Amino Acids, Branched-Chain; Energy Metabolism; Fatty Acids; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Organelle Biogenesis; Oxidative Phosphorylation; Signal Transduction
PubMed: 33013697
DOI: 10.3389/fendo.2020.00617