Organelles within cells are interconnected by physical associations or contact sites. In the last decade, many reports have shown that these interactions are functional domains that maintain cellular homeostasis. One of the best studied interactions is between endoplasmic reticulum (ER) and mitochondria via mitochondria-associated membranes or MAMs. MAMs are lipid rafts in the ER in close apposition to mitochondria, where multiple enzymatic activities converge to coordinately regulate cellular functions such as: the import of phosphatidylserine into mitochondria from the ER for decarboxylation to phosphatidylethanolamine, cholesterol esterification, calcium signaling, mitochondrial shape and motility, autophagy and apoptosis. In this chapter, we describe and discuss some of the methods to isolate and assay this interesting cellular region.
Dendritic and axonal plasticity, which mediates neurobiological recovery after a stroke, critically depends on the mitochondrial function of neurons. To investigate, in vivo, neuronal mitochondrial function at the stroke recovery stage, we employed Mito-tag mice combined with cerebral cortical infection of AAV9 produced from plasmids carrying Cre-recombinase controlled by two neuronal promoters, synapsin-I (SYN1) and calmodulin-kinase IIa to induce expression of a hemagglutinin (HA)-tagged enhanced green fluorescence protein (EGFP) that localizes to mitochondrial outer membranes of SYN1 positive (SYN) and CaMKIIa positive (CaMKIIa) neurons. These mice were then subjected to permanent middle cerebral artery occlusion (MCAO) and sacrificed 14 days post stroke.
While extensive work has examined the mechanisms of mitochondrial fission, it remains unclear whether internal mitochondrial proteins in metazoans play a direct role in the process. Previously, the yeast inner membrane protein Mdm33 was shown to be required for normal mitochondrial morphology and has been hypothesized to be involved in mitochondrial fission. However, it is unknown whether Mdm33 plays a direct role, and it is not thought to have a mammalian homolog.
Glioma is recognized as one of the most lethal and aggressive brain tumors. Although the standard-of-care treatment for glioblastoma (GBM) involves maximal surgical resection and temozolomide (TMZ) chemotherapy, the discovery of novel anti-tumor agents from nature sources is an effective strategy for glioma treatment. In this study, we conducted a screening process to identify the bisindole alkaloid melodinine J (MDJ) from Melodinus tenuicaudatus.
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Henry and Allison McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Introduction: We previously demonstrated that regulating mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) affects axonal Aβ generation in a well-characterized three-dimensional (3D) neural Alzheimer's disease (AD) model. MAMs vary in thickness and length, impacting their functions. Here, we examined the effect of MAM thickness on Aβ in our 3D neural model of AD.
Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Col. Belisario Domínguez-Sección XVI, Tlalpan, 14080, Mexico City, Mexico.
Cardiomyocyte senescence plays a crucial role in the pathophysiology of age-related cardiovascular disease. Senescent cells with impaired contractility, mitochondrial dysfunction, and hypertrophic growth accumulate in the heart during aging, contributing to cardiac dysfunction and remodeling. Mitochondrial dynamics is altered in aging cells, leading to changes in their function and morphology.
