Newborn and adult dog heart mitochondria were prepared from animals chronically adjusted to varying arterial oxygen tensions. Similarly, rat liver and heart mitochondria were isolated from animals acutely exposed to lowered inspired oxygen. After isolation, all mitochondrial samples were assayed under normoxic conditions. These experiments illustrated the following effects of oxygen on mitochondrial function: 1) respiratory activity in State 3 or in the uncoupled state increased after hypoxia and decreased after increased in vivo oxygenation; 2) similarly, the turnover of cytochrome oxidase increased in hypoxia and decreased after increased oxygenation; 3) after chronic hypoxia cytochrome oxidase, cytochrome c and b concentrations decreased per miligram of mitochondrial protein; 4) all mitochondrial preparations were well coupled and exhibited normal capabilities to perform oxidative phosphorylation. The data are interpreted to indicate sensitive control of mitochondrial respiratory capacities by oxygen in vivo.
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http://dx.doi.org/10.1152/ajplegacy.1976.231.6.1811 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.
View Article and Find Full Text PDFAutophagy
January 2025
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Postmitotic skeletal muscle critically depends on tightly regulated protein degradation to maintain proteomic stability. Impaired macroautophagy/autophagy-lysosomal or ubiquitin-proteasomal protein degradation causes the accumulation of damaged proteins, ultimately accelerating muscle dysfunction with age. While studies have demonstrated the complementary nature of these systems, their interplay at the organism levels remains poorly understood.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Neuroscience, City University of Hong Kong, Hong Kong, Hong Kong.
Introduction: Antisense oligonucleotides (ASOs) have shown promise in reducing amyloid precursor protein (APP) levels in neurons, but their effects in astrocytes, key contributors to neurodegenerative diseases, remain unclear. This study evaluates the efficacy of APP ASOs in astrocytes derived from an individual with Down syndrome (DS), a population at high risk for Alzheimer's disease (AD).
Methods: Human induced pluripotent stem cells (hiPSCs) from a healthy individual and an individual with DS were differentiated into astrocytes.
Chem Sci
January 2025
School of Biomedical Engineering, Shanghai Jiao Tong University Shanghai 200240 China
Intracellular viscosity is a critical microenvironmental factor in various biological systems, and its abnormal increase is closely linked to the progression of many diseases. Therefore, precisely controlling the release of bioactive molecules in high-viscosity regions is vital for understanding disease mechanisms and advancing their diagnosis and treatment. However, viscosity alone cannot directly trigger chemical reactions.
View Article and Find Full Text PDFIran J Basic Med Sci
January 2025
i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), 47012 Valladolid, Spain.
Objectives: While ketone bodies are not the main heart fuel, exercise may increase their uptake. Objectives: This study aimed to investigate the effect of 6-week endurance training and Pyruvate dehydrogenase kinase 4 )PDK4( inhibition on ketone bodies metabolism in the heart of diabetic rats with emphasis on the role of Peroxisome proliferator-activated receptor-gamma coactivator PGC-1alpha (PGC-1α).
Materials And Methods: Sixty male Wistar rats were divided into eight groups: healthy control group (CONT), endurance training group (TRA), diabetic group (DM), DM + EX group, Dichloroacetate (DCA) group, DM + DCA group, TRA + DCA group, and DM + TRA + DCA group.
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