Ayesha Saleem

University of Manitoba | UMN · Faculty of Kinesiology and Recreation Management

Endurance exercise-mediated multisystemic adaptations are known to mitigate metabolism-related disorders such as obesity and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanisms that promote crosstalk between organs and orchestrate the pro-metabolic effects of endurance exercise remain unclear. Exercise-induced release of p...

Background: Human genetic disorders and transgenic mouse models have shown that mitochondrial DNA (mtDNA) mutations and telomere dysfunction instigate the aging process. Epidemiologically, exercise is associated with greater life expectancy and reduced risk of chronic diseases. While the beneficial effects of exercise are well established, the mol...

Several studies have illustrated that the polymerase gamma mutator (PolG) mice have reduced mitochondrial content secondary to systemic mitochondrial dysfunction, and subsequently a lower capacity to perform aerobic respiration and endurance exercise. We sought to delineate the extent of glycolysis as a means of energy production in the PolG mice i...

Key points p53 is one of several important proteins that regulate the synthesis and function of mitochondria in muscle, and mice lacking p53 have impaired aerobic capacity. The role of p53 in response to physiological stress such as exercise has not been investigated. We demonstrate that acute exercise induces the translocation of p53 to mitochondr...

The purpose of this study was to evaluate the role of sirtuin 1 (SirT1) in exercise- and resveratrol (RSV)-induced skeletal muscle mitochondrial biogenesis. Using muscle-specific SirT1-deficient (KO) mice and a cell culture model of differentiated myotubes, we compared the treatment of resveratrol, an activator of SirT1, with that of exercise in in...

Regular exercise reduces tumor growth in vivo and in vitro, but the exact mechanisms have yet to be fully elucidated. We have previously shown that chronic contractile activity (CCA) increases the concentration of skeletal muscle-derived EVs, and these in turn increased mitochondrial biogenesis in myoblasts. Here, we hypothesized that skeletal musc...

The effect of chronic contractile activity (CCA) on the biophysical properties and functional activity of skeletal muscle extracellular vesicles (Skm-EVs) is poorly understood due to challenges in distinguishing Skm-EVs originating from exercising muscle in vivo. To address this, myoblasts were differentiated into myotubes, and electrically paced (...

Mitochondrial quality control is critical in muscle to ensure both contractile and metabolic function. Nix is a BCL-2 family member, mitophagy receptor, and has recently been implicated in muscle atrophy. Human GWAS suggests altered Nix expression could predispose individuals to manifestations of mitochondrial disease. To interrogate the role of Ni...

Over the past several years, I have been interacting with an increasing number of Iranian scientists, including those currently living in Iran as well as others who are being educated elsewhere or have independent positions outside of that country. In all circumstances, the resulting collaborations have extended my own knowledge and allowed me to c...

Exosomal release pathway and autophagy together maintain homeostasis and survival of cells under stressful conditions. Autophagy is a catabolic process through which cell entities, such as malformed biomacromolecules and damaged organelles, are degraded and recycled via the lysosomal-dependent pathway. Exosomes, a sub-type of extracellular vesicles...

Background: Exercise is associated with health benefits, including the prevention and management of obesity. However, heterogeneity in the adaptive response to exercise training exists. Our objective was to evaluate if changes in extracellular vesicles (EVs) after acute aerobic exercise were associated with the responder phenotype following 6-week...

Extracellular vesicles (EVs), released from all cells, are essential to cellular communication and contain biomolecular cargo that can affect recipient cell function. Studies on the effects of contractile activity (exercise) on EVs usually rely on plasma/serum-based assessments, which contain EVs from many different cells. To specifically character...

Extracellular vesicles (EVs) are small lipid membrane-bound structures that are secreted by all cells, and play a central role in cellular communication. EVs are released from skeletal muscle during exercise, but the effects of contractile activity on skeletal muscle-derived EVs (Skm-EVs) are poorly understood due to the challenges in distinguishin...

Extracellular vesicles (EVs) released from all cells, are essential to cellular communication, and contain biomolecular cargo that can affect recipient cell function. Studies on the effects of contractile activity (exercise) on EVs usually rely on plasma/serum-based assessments, which contain EVs from many different cells. To specifically character...

Systemic hypoxia is a common element in most perinatal emergencies and is a known driver of Bnip3 expression in the neonatal heart. Bnip3 plays a prominent role in the evolution of necrotic cell death, disrupting ER calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests a cardioprotective role for...

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological functio...

Exercise is associated with various health benefits, including the prevention and management of obesity and cardiometabolic risk factors. However, a strong heterogeneity in the adaptive response to exercise training exists. The objective of this study was to evaluate if changes in extracellular vesicles (EVs) after acute aerobic exercise (AE) were...

Systemic hypoxia is a common element in most perinatal emergencies and is a known driver of Bnip3 expression in the neonatal heart. Bnip3 plays a prominent role in the evolution of necrotic cell death, disrupting ER calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests a cardioprotective role for...

Extracellular vesicles (EVs) are membranous vesicles secreted by both prokaryotic and eukaryotic cells and play a vital role in intercellular communication. EVs are classified into several subtypes based on their origin, physical characteristics, and biomolecular makeup. Exosomes, a subtype of EVs, are released by the fusion of multivesicular bodie...

Extracellular vesicles (EVs) are membranous vesicles secreted by both prokaryotic and eukaryotic cells and play a vital role in intercellular communication. EVs are classified into several subtypes based on their origin, physical characteristics, and biomolecular makeup. Exosomes, a subtype of EVs, are released by the fusion of multivesicular bodie...

Extracellular vesicles (EVs) are membranous vesicles secreted by both prokaryotic and eukaryotic cells and play a vital role in intercellular communication. EVs are classified into several subtypes based on their origin, physical characteristics, and biomolecular makeup. Exosomes, a subtype of EVs, are released by the fusion of multivesicular bodie...

Asthma is the most common chronic disease in children. It is characterized by difficulty in breathing and chronic airway inflammation associated with narrowing of the airways, and airway hyperresponsiveness. If left untreated, asthma can lead to respiratory distress and even death. A number of medications are available and prescribed to manage asth...

Obesity is a progressive chronic disease that is defined by increased adiposity and dysregulated blood lipid and glucose profiles. This, coupled with insulin resistance and hypertension, leads to the development of the metabolic syndrome in obese patients. Furthermore, obesity correlates strongly with an elevated risk and progression of a number of...

A central focus of systems biology is the functional mapping of protein-protein interactions under physiological conditions. Here we describe MaGiCaL-BiFC, a lentivirus-based bimolecular fluorescence protein-fragment complementation approach for the high-throughput, genome-scale identification of protein-protein interactions in mammalian cells. Aft...

Intriguingly, endurance exercise, obviously a highly beneficial activity in mitigating various metabolic diseases, is intimately related to a transient production of reactive oxygen species (ROS). The natural purpose of the ROS-initiated repair appears to be merely the cleanup of the damage caused by the acute ROS pulse, whether it was caused by ex...

Recent research has suggested that transmembrane protein 65 (TMEM65) is localized within the inner mitochondrial membrane. Little else is known about its function. In this study we investigated the location and function of TMEM65. Further, we report the functional consequences of a novel homozygous splice variant (c.472+1G>A) in the TMEM65 gene in...

The mtDNA mutator mouse lacks the proofreading capacity of the sole mtDNA polymerase, leading to accumulation of somatic mtDNA mutations, and a profound premature aging phenotype including elevated oxidative stress and apoptosis, and reduced mitochondrial function. We have previously reported that endurance exercise alleviates the aging phenotype i...

Mitochondrial DNA (mtDNA) mutator mice express a mutated form of mtDNA polymerase gamma that results an accelerated accumulation of somatic mtDNA mutations in association with a premature aging phenotype. An exploratory metabolomic analysis of cortical metabolites in sedentary and exercised mtDNA mutator mice and wild-type littermate controls at 9-...

The ATP demand required for muscle development is accommodated by elevations in mitochondrial biogenesis, through the co-ordinated activities of the nuclear and mitochondrial genomes. The most important transcriptional activator of the mitochondrial genome is mitochondrial transcription factor A (Tfam); however, the regulation of Tfam expression du...

PolG mice have reduced mitochondrial oxidative capacity secondary to systemic mitochondrial dysfunction, and subsequently show exercise intolerance. While the deleterious effects on oxidative capacity in the PolG mice have been clearly documented, assessment of a compensatory increase in anaerobic capacity in PolG mice is lacking. Thus, we sought t...

Physical inactivity is a primary modifiable risk factor for obesity and type 2 diabetes (T2D), metabolic diseases that are rampant in both pediatric/adult populations. Endurance exercise has been shown to prevent/attenuate the onset and progression of obesity/T2D. We postulated that exercise mediated these pro‐metabolic effects on distal fat depots...

Physical inactivity is a primary modifiable risk factor for obesity and type 2 diabetes (T2D) – metabolic diseases that are rampant in pediatric and adult population. Endurance exercise has been shown to prevent and/or attenuate the onset and progression of obesity and T2D. The myokine 'irisin' (cleaved product of Fndc5 in response to endurance exe...

The purpose of this study was to investigate whether p53 regulates mitochondrial function via changes in mitochondrial protein import, complex IV assembly, or the expression of key proteins involved in mitochondrial dynamics and degradation. Mitochondria from p53 KO mice displayed ultra-structural alterations, and were more punctate in appearance....

An acute bout of exercise activates downstream signaling cascades that ultimately result in mitochondrial biogenesis. In addition to inducing mitochondrial synthesis, exercise also triggers the removal of damaged cellular material via autophagy, and of dysfunctional mitochondria through mitophagy. Here we investigated the necessity of p53 for the c...

Several studies have illustrated that the polymerase gamma mutator (PolG) mice have reduced mitochondrial content secondary to systemic mitochondrial dysfunction, and subsequently a lower capacity to perform aerobic respiration and endurance exercise. We sought to delineate the extent of glycolysis as a means of energy production in the PolG mice i...

The function Bax and/or Bak in constituting a gateway for mitochondrial apoptosis in response to apoptotic stimuli has been unequivocally demonstrated. However, recent work has suggested that Bax/Bak may have unrecognized non-apoptotic functions related to mitochondrial function in non-stressful environments. Wild type (WT) and Bax/Bak double knock...

Regular exercise can maintain skeletal muscle mass as we age. However, the molecular mechanisms that contribute to muscle health with exercise are incompletely defined. Recently, a group of three p53‐regulated proteins called Sestrins (Sesn1–3) have been identified. Whether these proteins are altered with age, or are induced by acute exercise in mu...

Introduction To Muscle Skeletal muscle constitutes ~ 40% of total body weight, and its primary function is to provide force and energy for locomotion, breathing, and postural support. It can also act as a source of heat production during cold-induced stress or exercise. Skeletal muscle is a highly adaptable tissue that exhibits a remarkable range o...

SALEEM, A., H.N. CARTER, S. IQBAL, and D.A. HOOD. Role of p53 within the regulatory network controlling muscle mitochondrial biogenesis. Exerc. Sport Sci. Rev., Vol. 39, No. 4, pp. 199-205, 2011. The tumor suppressor protein p53 is recognized to contribute significantly to the regulation of mitochondrial content. Mice without p53 have reduced endur...

p53 protein is important for basal and exercise‐induced mitochondrial biogenesis in skeletal muscle. As shown previously, pifithrin‐α (15 μM) a specific inhibitor of p53, reduced the AICAR‐induced increase in mitochondrial content in myoblasts. This demonstrates that p53 partly mediates AMPK‐induced mitochondrial adaptations. Here, we investigated...

Short-term and longitudinal studies have shown that endurance exercise training extends life expectancy and reduces risk for many chronic disorders, including obesity, insulin resistance and type 2 diabetes (Hawley, 2004). Endurance exercise training orchestrates numerous morphological and metabolic adaptations in skeletal muscle, including mitocho...

Our intent was to investigate the mechanisms driving the adaptive potential of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in young (6 mo) and senescent (36 mo) animals in response to a potent stimulus for organelle biogenesis. We employed chronic electrical stimulation (10 Hz, 3 h/day, 7 days) to induce contractile activity of ske...

Acute contractile activity of skeletal muscle initiates the activation of signaling kinases. This promotes the phosphorylation of transcription factors, leading to enhanced DNA binding and transcriptional activation and/or repression. The mRNA products of nuclear genes encoding mitochondrial proteins are translated in the cytosol and imported into...

p53 is a tumor suppressor protein that also plays a role in regulating aerobic metabolism. Since skeletal muscle is a major source of whole body aerobic respiration, it is important to delineate the effects of p53 on muscle metabolism. In p53 knockout (KO) mice, we observed diminished mitochondrial content in mixed muscle and lowered peroxisome pro...

The intent of the present study was to investigate the adaptive potential of skeletal muscle, as well as subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in young (6 mo) and senescent (36 mo) animals in response to a standard regimen of chronic contractile activity (CCA). The TA and EDL muscles of 6 and 36 mo F344XBN rats were chronical...

Evidence indicates that p53 plays a role in modulating apoptosis, cell‐cycle arrest and aerobic metabolism. Our goal was to evaluate the role of p53 in regulating basal and exercise‐induced apoptosis in skeletal muscle. p53 KO mice had impaired whole muscle cytochrome c oxidase (COX) activity and reduced intermyofibrillar (IMF) state 3 respiration....

During aging, skeletal muscle undergoes sarcopenia, a condition characterized by a loss of muscle cell mass and alterations in contractile function. The origin of these decrements is unknown, but evidence suggests that they can be partly attributed to mitochondrial dysfunction. To characterize the nature of this dysfunction, we investigated skeleta...