A5033192033- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Cardiac Ischemia and Reperfusion
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Muscle Physiology and Disorders
- Ion channel regulation and function
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Calcium signaling and nucleotide metabolism
- Cholinesterase and Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- GABA and Rice Research
- RNA regulation and disease
- Organ Transplantation Techniques and Outcomes
- Natural Antidiabetic Agents Studies
- Retinoids in leukemia and cellular processes
- Heart Failure Treatment and Management
- melanin and skin pigmentation
Neuroscience Institute
2017-2023
National Research Council
2017-2021
University of Padua
2005-2021
Istituto Nazionale di Fisica Nucleare, Sezione di Padova
2019
Universidade Federal de Ciências da Saúde de Porto Alegre
2016
Universidade Regional do Noroeste do Estado do Rio Grande do Sul
2016
National Academies of Sciences, Engineering, and Medicine
2013
Vollum Institute
2005
Oregon Health & Science University
2000
We have studied the properties of permeability transition pore (PTP) in mitochondria from liver mice where Ppif gene encoding for mitochondrial Cyclophilin D (CyP-D) had been inactivated. Mitochondria Ppif-/- no CyP-D and displayed a striking desensitization PTP to Ca2+, that opening required about twice Ca2+ load necessary open strain-matched, wild-type mitochondria. lacking were insensitive Cyclosporin A (CsA), which increased retention capacity only mice. The response ubiquinone 0,...
Mammalian mitochondria possess an inner membrane channel, the permeability transition pore (MTP), which can be inhibited by nanomolar concentrations of cyclosporin (CS) A. The molecular basis for MTP inhibition CSA remains unclear. Mitochondria also a matrix cyclophilin (CyP) with unique N-terminal sequence (CyP-M). To test hypothesis that it interacts MTP, we have studied interactions CyP-M rat liver Western blotting specific antibody against its N terminus. Although sonication in isotonic...
Blue native gel electrophoresis purification and immunoprecipitation of F(0)F(1)-ATP synthase from bovine heart mitochondria revealed that cyclophilin (CyP) D associates to the complex. Treatment intact with membrane-permeable bifunctional reagent dimethyl 3,3-dithiobis-propionimidate (DTBP) cross-linked CyPD lateral stalk ATP synthase, whereas no interactions F(1) sector subunits, natural inhibitor protein IF1, ATP/ADP carrier were observed. The synthase-CyPD have functional consequences on...
Multiple sclerosis (MS) is the leading cause of neurological disability in young adults, affecting some two million people worldwide. Traditionally, MS has been considered a chronic, inflammatory disorder central white matter which ensuing demyelination results physical [Frohman EM, Racke MK, Raine CS (2006) N Engl J Med 354:942-955]. More recently, become increasingly viewed as neurodegenerative neuronal loss, axonal injury, and atrophy CNS lead to permanent clinical disability. Although...
Energized mouse liver mitochondria displayed the same calcium retention capacity (a sensitive measure of propensity permeability transition pore (PTP) to open) irrespective whether phosphate, arsenate, or vanadate was permeating anion. Unexpectedly, however, phosphate specifically required for PTP desensitization by cyclosporin A (CsA) genetic inactivation cyclophilin D (CyP-D). Indeed, when replaced vanadate, bicarbonate, inhibitory effects CsA and CyP-D ablation on disappeared. After...
Mitochondria are key organelles for brain health. Mitochondrial alterations have been reported in several neurodegenerative disorders, including Alzheimer's disease (AD), and the comprehension of underlying mechanisms appears crucial to understand their relationship with pathology. Using multiple genetic, pharmacological, imaging, biochemical approaches, we demonstrate that, different familial AD cell models, mitochondrial ATP synthesis is affected. The defect depends on reduced pyruvate...
The BCL-2 family includes both proapoptotic (e.g., BAX and BAK) antiapoptotic BCL-X(L)) molecules. cell death-regulating activity of members appears to depend on their ability modulate mitochondrial function, which may include regulation the permeability transition pore (PTP). We examined function BCL-X(L) using genetic biochemical approaches in budding yeast because studies with suggest that act upon highly conserved components. In this study we found wild-type yeast, induced...
Cyclophilin D (CypD), a regulator of the mitochondrial membrane permeability transition pore (PTP), enhances Ca 2+ -induced permeabilization and cell death in brain. However, role CypD hypoxic-ischemic (HI) brain injury at different developmental ages is unknown. At postnatal day (P) 9 or P60, littermates CypD-deficient [knock-out (KO)], wild-type (WT), heterozygous mice were subjected to HI, was evaluated 7 d after HI. deficiency resulted significant reduction HI P60 but worsened P9. After...
Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy are inherited muscle disorders caused by mutations of genes encoding the extracellular matrix protein collagen VI (ColVI). Mice lacking ColVI (Col6a1(-/-)) display a myopathic phenotype associated with ultrastructural alterations mitochondria sarcoplasmic reticulum, mitochondrial dysfunction abnormal opening permeability transition pore (PTP) increased apoptosis fibers. Treatment cyclosporin (Cs) A, drug that desensitizes PTP...
Abstract Mitochondrial dysfunction is implicated in most neurodegenerative diseases, including Alzheimer's disease (AD). We here combined experimental and computational approaches to investigate mitochondrial health bioenergetic function neurons from a double transgenic animal model of AD (PS2APP/B6.152H). Experiments primary cortical demonstrated that had reduced respiratory capacity. Interestingly, the predicted this phenotype could not be explained by any defect chain (RC), but closely...
Abstract Ca 2+ handling by mitochondria is crucial for cell life and the direct measure of mitochondrial concentration in living cells pivotal interest. Genetically‐encoded indicators greatly facilitated this task, however they require demanding delivery procedures. On other hand, existing mitochondria‐targeted synthetic are plagued several drawbacks, example, non‐specific localization, leakage, toxicity. Here we report synthesis characterization a new fluorescent sensor, named mt‐fura‐2,...
We have studied the pathways for Ca2+ transport in mitochondria of fruit fly Drosophila melanogaster. demonstrate presence ruthenium red (RR)-sensitive uptake, RR-insensitive release, and Na+-stimulated release energized mitochondria, which match well characterized mammalian mitochondria. Following larger matrix loading underwent spontaneous an event that mammals is due to opening permeability transition pore (PTP). Like PTP mammals, Ca2+-induced could be triggered by uncoupler, diamide,...
Abstract Background Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for large number conditions. In this study, we have set up large-scale screening platform mitochondrial-based modulators with promising therapeutic potential. Results Using differentiated human neuroblastoma cells, screened 1200 FDA-approved compounds identified 61 molecules that significantly increased cellular ATP...
Mitochondria isolated from engineered mice lacking Cyclophilin D (CypD), a component of the Permeability Transition Pore (PTP) complex, can still undergo Ca2 + -dependent but Cyclosporin A-insensitive permeabilization inner membrane. Higher concentrations are required than for wild-type controls. The characteristics pore formed in this system were not known, and it has been proposed that they might differ substantially those normal PTP. To test hypothesis, we have characterized PTP isogenic...