A5003591293- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Muscle Physiology and Disorders
- ATP Synthase and ATPases Research
- Muscle metabolism and nutrition
- Metabolism and Genetic Disorders
- Cardiovascular and exercise physiology
- Cardiac Ischemia and Reperfusion
- Cardiovascular Function and Risk Factors
- Parkinson's Disease Mechanisms and Treatments
- Glycosylation and Glycoproteins Research
- Cardiovascular Effects of Exercise
- Respiratory Support and Mechanisms
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Galectins and Cancer Biology
- Signaling Pathways in Disease
- Electron Spin Resonance Studies
- Exercise and Physiological Responses
- Cardiomyopathy and Myosin Studies
- Histone Deacetylase Inhibitors Research
- Birth, Development, and Health
- Cardiac Fibrosis and Remodeling
- Protein Tyrosine Phosphatases
University of Ottawa
2017-2024
Université de Montréal
2007-2017
Shriners Hospitals for Children - Erie
2017
McGill University
2017
University of California, San Diego
2015
Albert Einstein College of Medicine
2015
University of Montana
2015
Burelle (France)
2015
Washington University in St. Louis
2013
Centre Hospitalier de l’Université de Montréal
2007
Rationale: The role of Parkin in hearts is unclear. Germ-line knockout mice have normal hearts, but protective cardiac ischemia. Parkin-mediated mitophagy reportedly either irrelevant, or a major factor, the lethal cardiomyopathy evoked by myocyte–specific interruption dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Objective: To understand and fission–defective adult mouse hearts. Methods Results: mRNA were present at low levels upregulated after myocyte–directed Drp1 gene...
Rationale: Mechanical ventilation (MV) is associated with adverse effects on the diaphragm, but cellular basis for this phenomenon, referred to as ventilator-induced diaphragmatic dysfunction (VIDD), poorly understood.Objectives: To determine whether mitochondrial function and energy status are disrupted in human diaphragms after MV, role of mitochondria-derived oxidative stress development VIDD.Methods: Diaphragm biceps specimens obtained from brain-dead organ donors who underwent MV...
Mitochondrial quality control plays a vital role in the maintenance of optimal mitochondrial function. However, its roles and regulation remain ill-defined cardiac pathophysiology. Here, we tested hypothesis that PARK2/Parkin, an E3-ligase recently described as being involved mitophagy, is important for (1) normal function; (2) adequate recovery from sepsis, condition known to induce reversible injury through poorly understood mechanisms. Investigations function were thus performed wild-type...
Key points Mitochondrial‐derived vesicle (MDV) formation occurs under baseline conditions and is rapidly upregulated in response to stress‐inducing H9c2 cardiac myoblasts. In mice of MDVs readily the heart normal healthy while mitophagy comparatively less prevalent. acute stress induced by doxorubicin, mitochondrial dysfunction develops heart, triggering MDV mitophagy. thus active system, where it probably constitutes a housekeeping mechanism first line defence against stress. Abstract The...
Rationale: Dysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and potential genetic mechanism cardiomyopathy. Despite epidemiological associations between heart failure, the role Parkin quality control in maintaining normal cardiac homeostasis poorly understood. Objective: We used germline mutants cardiac-specific RNA interference to interrogate regulation cardiomyocyte examine functional...
PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, was suggested as an important regulator of fiber type determination. However, whether a type-specific content exists, relates to basal levels content, such relationships are preserved between humans classically used rodent models all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the its...
Background Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, inefficient cellular components. No information available regarding degree sepsis-induced mitochondrial autophagy ventilatory locomotor muscles. This study tests hypotheses that are more prone injury, depressed biogenesis induction compared with Methodology/Principal Findings Adult...
Abstract Mitochondria play a crucial role in neuronal survival through efficient energy metabolism. In pathological conditions, mitochondrial stress leads to death, which is regulated by the anti-apoptotic BCL-2 family of proteins. MCL-1 an protein localized mitochondria either outer membrane (OM) or inner (Matrix), have distinct roles inhibiting apoptosis and promoting bioenergetics, respectively. While for Mcl1 well characterized, protective function Matrix remains poorly understood. Here,...
Parkin, an E3 ubiquitin ligase encoded by the Park2 gene, has been implicated in regulation of mitophagy, a quality control process which defective mitochondria are degraded. The exact physiological significance Parkin regulating mitochondrial function and contractility skeletal muscle remains largely unexplored. Using Park2-/- mice, we show that ablation causes decrease specific force, severe respiration, uncoupling increased susceptibility to opening permeability transition pore. These...
Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of muscle cells (MuSCs). We show MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive exit from deep quiescence. Deletion fusion protein OPA1 fragmentation transitions MuSCs into G-alert quiescence, causing premature depletion a stimulus. loss activates...
Abstract Mitochondria share attributes of vesicular transport with their bacterial ancestors given ability to form mitochondrial‐derived vesicles (MDVs). MDVs are involved in mitochondrial quality control and formation is enhanced stress may, therefore, play a potential role mitochondrial‐cellular communication. However, MDV proteomic cargo has remained mostly undefined. In this study, we strategically used an vitro budding/reconstitution assay on cardiac mitochondria, followed by graded...
Adaptation of myocardial energy substrate utilization may contribute to the cardioprotective effects regular exercise, a possibility supported by evidence showing that pharmacological metabolic modulation is beneficial ischemic hearts during reperfusion. Thus we tested hypothesis effect physical exercise on recovery from ischemia-reperfusion associated with protective phenotype. Function, glycolysis, and oxidation glucose, lactate, palmitate were measured in isolated working sedentary...
The diaphragm is a unique skeletal muscle designed to be rhythmically active throughout life, such that its sustained inactivation by the medical intervention of mechanical ventilation (MV) represents an unanticipated physiological state in evolutionary terms. Within short period after initiating MV, develops atrophy, damage, and diminished strength, many these features appear arise from mitochondrial dysfunction. Notably, response metabolic perturbations, mitochondria fuse, divide, interact...
Peripheral muscle alterations have been recognized to contribute disability in chronic obstructive pulmonary disease (COPD).To describe the mitochondrial phenotype a moderate severe COPD population and age-matched controls.Three primary aspects of function were assessed permeabilized locomotor fibers.Respiration rates per milligram fiber weight significantly lower compared with healthy control under various respiratory states. However, when variations volume taken into account by normalizing...
This study determined whether susceptibility to opening of the permeability transition pore (PTP) varies according muscle phenotype represented by slow oxidative soleus (Sol) and superficial white gastrocnemius (WG). Threshold for Ca2+-induced mitochondrial Ca2+ release following PTP was with a novel approach using permeabilized ghost myofibers. values were approximately threefold higher in fibers from WG compared those Sol (124+/-47 vs. 30.4+/-6.8 pmol Ca2+/mU citrate synthase). A similar...
Susceptibility of cardiomyocytes to stress-induced damage has been implicated in the development cardiomyopathy Duchenne muscular dystrophy, a disease caused by lack cytoskeletal protein dystrophin which heart failure is frequent. However, factors underlying progression are unclear and treatments limited. Here, we tested hypothesis greater susceptibility opening mitochondrial permeability transition pore (PTP) hearts from young dystrophic (mdx) mice (before overt cardiomyopathy) when...
Key points Mitochondria are increasingly implicated in the pathogenesis of Duchenne muscular dystrophy (DMD). However, extent to which multiple facets mitochondrial function altered remains uncertain due lack detailed assessment. Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α) was recently shown improve muscle pathology dystrophic muscle. mechanisms not fully elucidated. This study provides novel information on dysfunction DMD namely that (i) loss biomass...
Autophagy is an important proteolytic pathway in skeletal muscles. The roles of muscle fiber type composition and oxidative capacity remain unknown relation to autophagy. diaphragm (DIA) a fast-twitch with high capacity, the tibialis anterior (TA) low soleus (SOL) slow-twitch capacity. We hypothesized that major determinant autophagy Following acute (24 h) starvation adult C57/Bl6 mice, each was assessed for compared controls. measured by monitoring autophagic flux following leupeptin (20...