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Dive into the research topics where Lucas A. Maddalena is active.

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Featured researches published by Lucas A. Maddalena.


Longevity & Healthspan | 2014

A midlife crisis for the mitochondrial free radical theory of aging

Jeffrey A. Stuart; Lucas A. Maddalena; Max Merilovich; Ellen L. Robb

Since its inception more than four decades ago, the Mitochondrial Free Radical Theory of Aging (MFRTA) has served as a touchstone for research into the biology of aging. The MFRTA suggests that oxidative damage to cellular macromolecules caused by reactive oxygen species (ROS) originating from mitochondria accumulates in cells over an animal’s lifespan and eventually leads to the dysfunction and failure that characterizes aging. A central prediction of the theory is that the ability to ameliorate or slow this process should be associated with a slowed rate of aging and thus increased lifespan. A vast pool of data bearing on this idea has now been published. ROS production, ROS neutralization and macromolecule repair have all been extensively studied in the context of longevity. We review experimental evidence from comparisons between naturally long- or short-lived animal species, from calorie restricted animals, and from genetically modified animals and weigh the strength of results supporting the MFRTA. Viewed as a whole, the data accumulated from these studies have too often failed to support the theory. Excellent, well controlled studies from the past decade in particular have isolated ROS as an experimental variable and have shown no relationship between its production or neutralization and aging or longevity. Instead, a role for mitochondrial ROS as intracellular messengers involved in the regulation of some basic cellular processes, such as proliferation, differentiation and death, has emerged. If mitochondrial ROS are involved in the aging process, it seems very likely it will be via highly specific and regulated cellular processes and not through indiscriminate oxidative damage to macromolecules.


Carbohydrate Research | 2016

Microwave-assisted syntheses of BODIPY-sugar conjugates through click chemistry and conjugate assembly into liposomes.

Ravi Shekar Yalagala; Sina Atrin Mazinani; Lucas A. Maddalena; Jeffrey A. Stuart; Fengyang Yan; Hongbin Yan

BODIPY fluorophores bearing azide or terminal alkyne functions were conjugated with glycans modified with terminal alkyne or azido through the Cu(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) chemistry under microwave heating while these reactions did not proceed when heated in an oil-bath. The BODIPY-glycan conjugate product 8a undergoes self-assembly into liposomes when hydrated. Formation of liposomes was confirmed by both bright field and confocal microscopy. Fluorescent emission within the liposome was shifted from green to red due to effective high concentrations.


Biochimica et Biophysica Acta | 2017

The mitochondria-targeted imidazole substituted oleic acid ‘TPP-IOA’ affects mitochondrial bioenergetics and its protective efficacy in cells is influenced by cellular dependence on aerobic metabolism

Lucas A. Maddalena; Mikel Ghelfi; Jeffrey Atkinson; Jeffrey A. Stuart

A variety of mitochondria-targeted small molecules have been invented to manipulate mitochondrial redox activities and improve function in certain disease states. 3-Hydroxypropyl-triphenylphosphonium-conjugated imidazole-substituted oleic acid (TPP-IOA) was developed as a specific inhibitor of cytochrome c peroxidase activity that inhibits apoptosis by preventing cardiolipin oxidation and cytochrome c release to the cytosol. Here we evaluate the effects of TPP-IOA on oxidative phosphorylation in isolated mitochondria and on mitochondrial function in live cells. We demonstrate that, at concentrations similar to those required to achieve inhibition of cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation in isolated mitochondria. In live SH-SY5Y cells, TPP-IOA partially collapsed mitochondrial membrane potential, caused extensive fragmentation of the mitochondrial network, and decreased apparent mitochondrial abundance within 3h of exposure. Many cultured cell lines rely primarily on aerobic glycolysis, potentially making them less sensitive to small molecules disrupting oxidative phosphorylation. We therefore determined the anti-apoptotic efficacy of TPP-IOA in SH-SY5Y cells growing in glucose or in galactose, the latter of which increases reliance on oxidative phosphorylation for ATP supply. The anti-apoptotic activity of TPP-IOA that was observed in glucose media was not seen in galactose media. It therefore appears that, at concentrations required to inhibit cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation. In light of these data it is predicted that potential future therapeutic applications of TPP-IOA will be restricted to highly glycolytic cell types with limited reliance on oxidative phosphorylation.


Acta Histochemica | 2017

A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture

Andrew Valente; Lucas A. Maddalena; Ellen L. Robb; Fereshteh Moradi; Jeffrey A. Stuart


Biochemical and Biophysical Research Communications | 2017

Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2.

Ellen L. Robb; Fereshteh Moradi; Lucas A. Maddalena; Andrew Valente; Joao Fonseca; Jeffrey A. Stuart


Comparative Biochemistry and Physiology A-molecular & Integrative Physiology | 2012

Absence of metabolic rate allometry in an ex vivo model of mammalian skeletal muscle

Ellen L. Robb; Lucas A. Maddalena; Valerie A. Dunlop; Tamara Foster; Jeffrey A. Stuart


Biochemical and Biophysical Research Communications | 2017

Hydrogen peroxide production is affected by oxygen levels in mammalian cell culture

Lucas A. Maddalena; Shehab M. Selim; Joao Fonseca; Holt Messner; Shannon McGowan; Jeffrey A. Stuart


Free Radical Biology and Medicine | 2017

Neuroglobin Overexpression Promotes Mitochondrial Fusion and Prevents Mitochondrial Network Fragmentation in SHSY5Y Cells Subjected to Pro-apoptotic Conditions

Marco Fiocchetti; Lucas A. Maddalena; Fereshteh Moradi; Joao Couto Fonseca; Mohamed Rezk; Ryan Hallam; Gregory M.J. Foran; Aleksandar Necakov; Maria Marino; Jeffrey A. Stuart


Free Radical Biology and Medicine | 2017

Estradiol and Estrogen Receptor-β Agonist Diarylpropionitrile Promote Mitochondrial Network fusion

Fereshteh Moradi; Lucas A. Maddalena; Jeffrey Allan Stuart; Joao Couto Fonseca


Free Radical Biology and Medicine | 2015

A Mitochondria-Targeted Anti-Apoptotic Inhibitor of Cytochrome C Peroxidase Activity Interferes with Mitochondrial Bioenergetics and Does Not Prevent Cell Death in Cultured Cells Reliant on Aerobic Metabolism

Lucas A. Maddalena; Jeffrey Atkinson; Jeffrey A. Stuart

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