Review
Biochemistry & Molecular Biology
Hae-Jeong Park, Inyeong Choi, Kang-Hyun Leem
Summary: Postmortem studies have shown that schizophrenia patients have lower brain pH levels, with implications for the role of this phenomenon in disease progression being discussed in depth. Changes in mitochondrial morphology and function in schizophrenia patients may contribute to abnormal metabolism. Alterations in pH levels could have effects on neuronal activity and pathophysiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biology
Yury D. Nechipurenko, Denis A. Semyonov, Igor A. Lavrinenko, Denis A. Lagutkin, Evgenii A. Generalov, Anna Y. Zaitceva, Olga Matveeva, Yegor E. Yegorov
Summary: This article summarizes recent studies linking acidosis with severe COVID-19 cases. It highlights the vicious cycle between acidosis and hypoxia in COVID-19 patients, which can exacerbate the condition. The review suggests the importance of supporting normal blood pH in COVID-19 therapy.
Article
Agriculture, Dairy & Animal Science
Zhongyan Lu, Lingmeng Kong, Shenhao Ren, Jorg R. Aschenbach, Hong Shen
Summary: The rapid accumulation of organic acids, particularly lactate, is believed to be the main cause of ruminal acidosis (RA) in ruminants fed high-concentrate diets. However, the mechanisms behind this phenomenon are still not well understood. This study investigated the changes in ruminal microbiome and acidosis in goats fed diets with increasing concentrate portions. The results showed that an increase in dietary concentrate led to a sharp decrease in the abundance and expression of genes encoding lactate dehydrogenase, which is responsible for the conversion of pyruvate to lactate. These changes were attributed to specific bacterial groups and have important implications for the prevention of ruminal acidosis.
Article
Cardiac & Cardiovascular Systems
Alexander S. Milliken, Jessica H. Ciesla, Sergiy M. Nadtochiy, Paul S. Brookes
Summary: Tissue ischemia leads to acidic intracellular pH and the effect of acidic pH on metabolism is not well understood. This study used LCMS based targeted metabolomics to analyze the metabolic changes in perfused mouse hearts exposed to various conditions. It was found that acidic pH increased glycolysis metabolites and enhanced the glutathione redox state. Acidic pH reperfusion also induced significant metabolic changes, including elevated glycolysis metabolites, preservation of purine nucleotides, and enhancement of glutathione redox state. However, hypotheses regarding the mechanisms of cardioprotection by acidic pH reperfusion were not supported. In contrast, analysis of cardiac effluents suggested that mildly acidic pH may enhance succinate release during reperfusion. Overall, acidic pH is an independent metabolic regulator regardless of its location in the cell membrane.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Article
Chemistry, Organic
Imran Verirsen, Busra Uyar, Nezahat Gokce Ozsamur, Naime Demirok, Sundus Erbas-Cakmak
Summary: A structurally simple, tyrosinase-activatable photosensitizer based on pyridinium BODIPY has been developed, with selective cytotoxic singlet oxygen generation. The study demonstrates the potential of this photosensitizer in tissue-selective therapies.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Analytical
Ririko Nakaoka, Kazuhiro Kato, Kumiko Yamamoto, Hironobu Yasui, Shingo Matsumoto, Igor A. Kirilyuk, Valery V. Khramtsov, Osamu Inanami, Hiroshi Hirata
Summary: Extracellular acidification is a hallmark of tumor malignancy, and non-invasive mapping of extracellular pH (pHe) is essential for understanding the tumor microenvironment and monitoring tumor response to metabolism-targeting drugs. A modified electron paramagnetic resonance (EPR) system achieves higher sensitivity in mapping pHe and can be used to monitor the response of other metabolism-targeting drugs.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yukai Jing, Li Luo, Ying Chen, Lisa S. Westerberg, Peng Zhou, Zhiping Xu, Andres A. Herrada, Chan-Sik Park, Masato Kubo, Heng Mei, Yu Hu, Pamela Pui-Wah Lee, Bing Zheng, Zhiwei Sui, Wei Xiao, Quan Gong, Zhongxin Lu, Chaohong Liu
Summary: SARS-CoV-2 infection causes changes in the immune phenotype of B cells in recovered COVID-19 patients, with reduced CD19 expression and disrupted immune regulation, providing a new target for treating COVID-19.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Chemistry, Multidisciplinary
Zhichao Liu, Zhonghui Zhang, Yuandong Liu, Yuxiao Mei, Enduo Feng, Yangyi Liu, Tingting Zheng, Jinquan Chen, Sanjun Zhang, Yang Tian
Summary: The development of a novel tool for real-time monitoring and simultaneous quantitation of multiple molecules in mitochondria in freely moving animals is crucial for understanding the roles of mitochondria in brain functions. The study utilized a Raman fiber photometry to track and quantify mitochondrial O-2(.-), Ca2+, and pH in different brain regions, revealing changes in these parameters from superficial to deep brain regions during hypoxia. Furthermore, it was discovered that hypoxia-induced mitochondrial O-2(.-) burst was regulated by ASIC1a, leading to mitochondrial Ca2+ overload attributed to the influx of extracellular Ca2+.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biochemistry & Molecular Biology
Edward Caddye, Julien Pineau, Joshua Reyniers, Itamar Ronen, Alessandro Colasanti
Summary: Lactate, as a metabolic intermediate, shows potential as a biomarker for neurometabolic dysfunction in psychiatric disorders. Lactate response reflects metabolic and mitochondrial health, its concentration is regulated by the sleep-wake cycle, and it integrates and transmits information about arousal behaviors and cellular metabolism.
Article
Physiology
Lyvia R. Bowering, Tristan J. McArley, Jules B. L. Devaux, Anthony J. R. Hickey, Neill A. Herbert
Summary: This study investigated the impacts of climate change stressors on the Australasian snapper in New Zealand. The results showed that the snapper's metabolic performance remained high even in warm conditions, and they were able to adapt well to hypoxia. Therefore, despite the threat climate change poses to marine organisms, a temperature of 25°C may be metabolically optimal for the Australasian snapper in Northern New Zealand.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cell Biology
Sagar S. Manoli, Kyle Kisor, Bradley A. Webb, Diane L. Barber
Summary: The study found that increased NHE1 activity and pHi do not lead to increased glycolysis and decreased mitochondrial oxidative phosphorylation in clonal pancreatic and breast cancer cells. Additionally, EIPA causes a decrease in oxidative phosphorylation and changes in mitochondrial dynamics, including an increase in fusion. These findings contradict current paradigms and raise questions about the use of EIPA-like compounds to limit metabolic reprogramming in cancer cells.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Medicine, General & Internal
Jae Hyoung Im, Jin-Soo Lee, Moon-Hyun Chung, Hea Yoon Kwon, Man-Jong Lee, Ji Hyeon Baek
Summary: Regular monitoring of serum lactate in patients treated with linezolid is recommended, as it can lead to early detection of lactatemia and improve the detection rate of critical illnesses, enabling rapid rescue.
Article
Biochemistry & Molecular Biology
Martina Koncosova, Nikola Vrzackova, Ivana Krizova, Petra Tomasova, Silvie Rimpelova, Ales Dvorak, Libor Vitek, Michaela Rumlova, Tomas Ruml, Jaroslav Zelenka
Summary: Metabolic transformation in cancer cells leads to lactate accumulation and acidification in the tumor microenvironment, affecting cancer progression and patient prognosis. Cells adapted to acidosis are sensitive to oxidative damage, with lactate concentrations playing a role in sensitization. The drug CPI-613 can selectively eradicate acidosis-adapted cancer cells and the use of tetracycline can enhance its cytotoxic effect. Lactate metabolism in the Krebs cycle restores antioxidant capacity under acidosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Min Hu, Joseph M. Santin
Summary: This study investigates the reorganization of the metabolic transcriptional network in the brainstem of American bullfrogs during hibernation to achieve ischemia tolerance. The results suggest that improving neural performance during ischemia involves a transcriptional program for glycogen and glucose metabolism.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Neurosciences
Daniel A. Kane, Alexander C. Y. Foo, Erin B. Noftall, Karen Brebner, D. Gerrard Marangoni
Summary: Lactate, as the end product of glycolysis, plays various physiological roles by traveling within and between cells. However, its application to physical bioenergetics has been underexplored. This study suggests that lactate shuttling, as an allostatic thermoregulatory strategy, mitigates the consequences of elevated metabolic heat by exchanging extracellular lactate between tissues. The results of experiments on rat cortical brain samples support this hypothesis by showing lower heat and respiratory oxygen consumption rates during lactate-linked respiration compared to pyruvate-linked respiration.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Cell Biology
Troy L. Merry, Caitlin MacRae, Toan Pham, Christopher P. Hedges, Michael Ristow
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2020)
Article
Cell Biology
Randall F. D'Souza, Jonathan S. T. Woodhead, Christopher P. Hedges, Nina Zeng, Junxiang Wan, Hiroshi Kumagai, Changhan Lee, Pinchas Cohen, David Cameron-Smith, Cameron J. Mitchell, Troy L. Merry
Article
Ecology
F. Farhat, B. Simon, A. Amerand, J. Devaux, M. Belhomme, P. Calves, C. Moisan
ENVIRONMENTAL BIOLOGY OF FISHES
(2020)
Article
Physiology
Jonathan S. T. Woodhead, Randall F. D'Souza, Christopher P. Hedges, Junxiang Wan, Michael Berridge, David Cameron-Smith, Pinchas Cohen, Anthony J. R. Hickey, Cameron J. Mitchell, Troy L. Merry
JOURNAL OF APPLIED PHYSIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Christopher P. Hedges, Jordi Boix, Jagdish K. Jaiswal, Bhoopika Shetty, Peter R. Shepherd, Troy L. Merry
Summary: BYL719 delivered through diet effectively suppresses insulin signaling and maintains long-term efficacy without affecting food intake and other physiological indicators.
Article
Physiology
Alessandra Ferri, Xu Yan, Jujiao Kuang, Cesare Granata, Rodrigo S. F. Oliveira, Christopher P. Hedges, Adriano E. Lima-Silva, Francois Billaut, David J. Bishop
Summary: The study found that 15 days of moderate hypoxia exposure did not significantly alter mitochondrial respiration, genes, and proteins associated with mitochondrial biogenesis in young recreationally active males. However, an increase in mitochondrial protease LON content after hypoxia exposure suggests possible adaptations to optimize respiratory chain function under reduced oxygen availability.
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Randall F. D'Souza, Stewart W. C. Masson, Jonathan S. T. Woodhead, Samuel L. James, Caitlin MacRae, Christopher P. Hedges, Troy L. Merry
Summary: Inhibition of the primary neutrophil protease, neutrophil elastase, with A1AT can improve insulin sensitivity and glucose homeostasis in mice fed a high-fat diet. This improvement is associated with enhanced insulin-induced IRS-1 phosphorylation and reduced inflammation markers in white adipose tissue, highlighting the role of neutrophils in mediating diet-induced peripheral tissue insulin resistance.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Multidisciplinary Sciences
Jaime R. Willis, Anthony J. R. Hickey, Jules B. L. Devaux
Summary: Temperature is a key factor affecting all levels of organization in organisms, with even minute shifts from thermal optima leading to detrimental effects on growth, reproduction, and survival. Ectotherms are particularly sensitive to temperature changes, especially intertidal species, which often experience negative impacts on energetic processes. Studies have shown that during acute heat stress, mitochondrial function in the heart plays a crucial role in determining thermal tolerance, while the brain, being one of the most metabolically active and temperature-sensitive organs, faces an energetic crisis as temperatures rise.
SCIENTIFIC REPORTS
(2021)
Review
Biophysics
Tony Hickey, Jules Devaux, Vijay Rajagopal, Amelia Power, David Crossman
Summary: During the Carboniferous period, insects developed flight capabilities, with the evolution of specialized flight muscles called FMs. These FMs have unique adaptations for high frequency flight, but also present paradoxes and unanswered questions regarding their function and optimization.
BIOPHYSICAL REVIEWS
(2022)
Article
Biology
James Robertson, Andrew Jeffs, Christopher Hedges, Anthony J. R. Hickey
Summary: Isoeugenol, an anaesthetic used in the transportation of live lobsters, acts as a metabolic suppressant, reducing energy expenditure and improving survival rates. This study investigates the impact of isoeugenol on mitochondrial function, with a particular focus on respiration supported by complex I and cytochrome c oxidase. The results demonstrate that isoeugenol inhibits respiration through complex I and indicates it may act as a possible target for isoeugenol's effects.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2022)
Article
Physiology
Jules B. L. Devaux, Chris P. Hedges, Nigel Birch, Neill Herbert, Gillian M. C. Renshaw, Anthony J. R. Hickey
Summary: This study shows that intertidal triplefin fish species are able to better manage electron transfer within the ETS, resulting in reduced ROS production during hypoxic-hyperoxic transitions. This is likely due to their repeated exposure to extreme O2 fluctuations and the evolution of adaptive strategies.
JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMS AND ENVIRONMENTAL PHYSIOLOGY
(2023)
Article
Biology
Alice R. Harford, Jules B. L. Devaux, Anthony J. R. Hickey
Summary: Oxygen is essential for eukaryotic lifeforms, but fluctuations in O2 levels can cause harmful physiological changes and cell death. However, some species have evolved mechanisms to tolerate low oxygen levels. This study investigated the mitochondrial function of three fish species with varying degrees of hypoxia tolerance, revealing their ability to withstand low oxygen conditions.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2023)
Article
Physiology
Lyvia R. Bowering, Tristan J. McArley, Jules B. L. Devaux, Anthony J. R. Hickey, Neill A. Herbert
Summary: This study investigated the impacts of climate change stressors on the Australasian snapper in New Zealand. The results showed that the snapper's metabolic performance remained high even in warm conditions, and they were able to adapt well to hypoxia. Therefore, despite the threat climate change poses to marine organisms, a temperature of 25°C may be metabolically optimal for the Australasian snapper in Northern New Zealand.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Physiology
Randall F. D'Souza, Vandre C. Figueiredo, James F. Markworth, Nina Zeng, Christopher P. Hedges, Llion A. Roberts, Truls Raastad, Jeff S. Coombes, Jonathan M. Peake, Cameron J. Mitchell, David Cameron-Smith
Summary: Cold water immersion (CWI) affects muscle adaptations to exercise training by modulating miRNA expression, with attenuated muscle hypertrophy and increased angiogenesis. This study examined the regulatory mechanisms involved in cleavage and nuclear export of mature miRNA, and found that CWI suppressed mRNA expression of DROSHA, EXPORTIN-5, and DICER in skeletal muscle. MiR-133a and miR-126 remained elevated at 24 hours post-exercise only in the CWI trial. However, the gene targets of these miRNA did not differ between trials.
PHYSIOLOGICAL REPORTS
(2023)
Article
Biology
Jules B. L. Devaux, Anthony J. R. Hickey, Gillian M. C. Renshaw
Summary: Anoxia/re-oxygenation (AR) can cause irreversible brain damage due to elevated oxidative stress. Two shark species, the epaulette shark and the grey carpet shark, have adapted to survive AR without significant brain injuries. The epaulette shark shows the capacity to suppress metabolism and depress succinate oxidation, resulting in lower ROS production compared to the grey carpet shark. The research sheds light on potential mechanisms to mitigate brain injury during AR.