A5012700012- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Muscle Physiology and Disorders
- Metabolism, Diabetes, and Cancer
- Muscle metabolism and nutrition
- Genetics, Aging, and Longevity in Model Organisms
- Exercise and Physiological Responses
- PI3K/AKT/mTOR signaling in cancer
- ATP Synthase and ATPases Research
- Diet and metabolism studies
- Genetic Neurodegenerative Diseases
- Cardiac Ischemia and Reperfusion
- Alzheimer's disease research and treatments
- Genomics, phytochemicals, and oxidative stress
- CRISPR and Genetic Engineering
- Coenzyme Q10 studies and effects
- Cardiovascular and exercise physiology
- High Altitude and Hypoxia
- Neuroinflammation and Neurodegeneration Mechanisms
- Health, Environment, Cognitive Aging
- Biochemical Analysis and Sensing Techniques
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Extracellular vesicles in disease
- Spaceflight effects on biology
Virginia Tech
2020-2024
University of Virginia
2015-2022
Cardiovascular Research Center
2019
Colorado State University
2012-2015
University at Buffalo, State University of New York
2011
West Virginia University
2010
Abstract Mitochondrial health is critical for skeletal muscle function and improved by exercise training through both mitochondrial biogenesis removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes oxidative stress at 3–12 h 6 post-exercise muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer , allows...
Significance Here, we present unequivocal evidence of physical association AMPK holoenzymes with mitochondrial reticulum (mitoAMPK) across multiple mouse tissues conservation in human skeletal muscle and heart. We demonstrate that mitoAMPK is activated heterogeneously the by energetic stress. Finally, suggests activation required for mitophagy. propose responds to microenvironment cues maintain homeostasis through quality control.
Chronic inhibition of the protein synthesis regulator mTORC1 through rapamycin extends life span in mice, with longer extension females than males. Whether treatment inhibits or whether it does so differently between sexes has not been examined. UM-HET3 mice were fed a control rapamycin-supplemented (Rap) diet for 12 weeks. Protein mixed, cytosolic (cyto), and mitochondrial (mito) fractions DNA signaling determined skeletal muscle, heart, liver. In both sexes, mito was maintained muscle from...
Our understanding of the molecular mechanisms underlying adaptations to resistance exercise remains elusive despite significant biological and clinical relevance. We developed a novel voluntary mouse weightlifting model, which elicits squat-like activities against adjustable load during feeding, investigate exercise-induced contractile metabolic adaptations. RNAseq analysis revealed that single bout induced transcriptome responses genes function in posttranslational modification, metabolism,...
Assessment of structural and functional changes mitochondria is vital for biomedical research as are the power plants essential biological processes tissue/organ functions. Others we have developed a novel reporter gene, pMitoTimer, which codes redox sensitive mitochondrial targeted protein that switches from green fluorescence (GFP) to red fluorescent (DsRed) when oxidized. It has been shown in transfected cells, transgenic C. elegans Drosophila m., well somatically adult skeletal muscle...
Maintenance of mitochondrial quality is essential for skeletal muscle function and overall health. Exercise training elicits profound adaptations to mitochondria improve in muscle. We have recently demonstrated that acute exercise promotes removal damaged/dysfunctional via mitophagy during recovery through the Ampk-Ulk1 signaling cascade. In this Extra View, we explore whether Pink1 stabilized on following as signal mitophagy. observed no discernable presence isolated from at any time point...
Summary Maintaining proteostasis is thought to be a key factor in slowed aging. In several growth‐restricted models of long‐life, we have shown evidence increased proteostatic mechanisms, suggesting that may shared characteristic The Snell dwarf mouse generated through the mutation Pit‐1 locus causing reductions multiple hormonal growth factors and mTORC 1 signaling. dwarfs are one longest lived rodent We hypothesized mechanisms would compared control (Con) as other Using D 2 O,...
Abstract Background Succinate dehydrogenase (Complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate mitochondrial Krebs cycle and transferring electrons from ubiquinone electron transport chain (ETC). Mutations Complex II are associated with number pathologies. SDHD, one four subunits II, serves anchoring complex inner-membrane ubiquinone. Thus, modeling SDHD dysfunction could be valuable tool for understanding its importance metabolism developing...
Increasing mouse litter size [crowded (CL)] presumably imposes a transient nutrient stress during suckling and extends lifespan through unknown mechanisms. Chronic calorically restricted rapamycin-treated mice have decreased DNA synthesis mTOR complex 1 (mTORC1) signaling but maintained protein synthesis, suggesting maintenance of existing cellular structures. We hypothesized that CL would exhibit similar synthetic responses to other long-lived models and, by comparing new DNA, insight may...
The aim of this study was to determine the effect 14 days 5-aminoimidazole-4-carboxamide-1β-4-ribofuranoside (AICAR) treatment on mammalian target rapamycin (mTOR) signaling and mTOR-regulated processes (i.e., translation initiation) in obese mouse skeletal muscle. Our hypothesis that daily (14 days) with AICAR would normalize obesity-induced alterations muscle mTOR lean levels positively affect mass. Fourteen-week-old male, (L; 31.3 g body wt) wild-type ob/ob (O; 59.6 mice were injected...
Red blood cell (RBC)-derived adenosine triphosphate (ATP) has been proposed as an integral component in the regulation of oxygen supply to skeletal muscle. In ex vivo settings RBCs have shown release ATP response a number stimuli, including stimulation adrenergic receptors. Further evidence suggested that from was dependent on activation adenylate cyclase (AC)/cyclic monophosphate (cAMP)-dependent pathways and involved pannexin 1 (Panx1) channel. Here we show express Panx1 confirm its...
The Alaskan Husky has been specifically bred for endurance performance and is capable of extreme performance. We examined sled dogs in the trained state at beginning race season after a 1,600-km (Iditarod). Our hypothesis was that lipids would be predominant substrate during submaximal exercise long-distance racing dogs, increase reliance on an bout same absolute intensity. experiments were completed over three testing periods, which January two different years before participation race, or...
Functional impairment is a major concern in the obese population, leading to reductions everyday activities [1]. Obesity-related muscle function are due loss of mass (i.e. sarcopenia), which occurs largely from an imbalance between rates protein synthesis and degradation [2,3]. A controlling mechanism for peptide/protein formation messenger RNA (mRNA) translation. Initiation translation regulated by hormones diet through alterations mammalian Target Rapamycin (mTOR) [4,5,6]. Despite...
Deterioration of neuromuscular junction (NMJ) integrity and function is causal to muscle atrophy frailty, ultimately hindering quality life increasing the risk death. In particular, NMJ vulnerable ischemia reperfusion (IR) injury when blood flow restricted followed by restoration. However, little known about underlying mechanism(s) hence lack effective interventions. New evidence suggests that mitochondrial oxidative stress plays a role in IR injury, which can be precluded enhancing protein...
Abstract Alzheimer’s disease (AD) develops along a continuum that spans years prior to diagnosis. Decreased muscle function and mitochondrial respiration occur earlier in those develop AD; however, it is unknown what causes these peripheral phenotypes of the brain. Exercise promotes muscle, mitochondria, cognitive health proposed be potential therapeutic for AD, but no study has investigated how skeletal adapts exercise training an AD-like context. Utilizing 5xFAD mice, AD model ad-like...
Metabolism regulates neuronal activity and modulates the occurrence of epileptic seizures. Here, using two rodent models absence epilepsy, we show that hypoglycaemia increases spike-wave We then selectively disrupting glycolysis in thalamus, a structure implicated is sufficient to increase propose activation thalamic AMP-activated protein kinase, sensor cellular energetic stress potentiator metabotropic GABAB-receptor function, significant driver hypoglycaemia-induced kinase augments...
Ischemia-reperfusion (IR) due to temporary restriction of blood flow causes tissue/organ damages under various disease conditions, including stroke, myocardial infarction, trauma, and orthopedic surgery. In the limbs, IR injury motor nerves muscle fibers reduced mobility quality life. Endurance exercise training has been shown increase tissue resistance numerous pathological insults. To elucidate impact endurance on in skeletal muscle, sedentary exercise-trained mice (5 wk voluntary running)...