A5009607029- Mitochondrial Function and Pathology
- Cellular transport and secretion
- ATP Synthase and ATPases Research
- Retinal Development and Disorders
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Metabolism and Genetic Disorders
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Slime Mold and Myxomycetes Research
- Ubiquitin and proteasome pathways
- Retinal Diseases and Treatments
- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Calcium signaling and nucleotide metabolism
- Adenosine and Purinergic Signaling
- Photosynthetic Processes and Mechanisms
- Genomics and Phylogenetic Studies
- Photoreceptor and optogenetics research
- Cellular Mechanics and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Neurological Disease Mechanisms and Treatments
- Protist diversity and phylogeny
- Erythrocyte Function and Pathophysiology
- Liver physiology and pathology
Johns Hopkins Medicine
2015-2024
Johns Hopkins University
2015-2024
St. Jude Children's Research Hospital
2024
Howard Hughes Medical Institute
2023
University of Copenhagen
2023
University of Wisconsin–Madison
2023
The University of Tokyo
2009-2011
Ochanomizu University
2005-2011
Nagoya University
2009-2011
Abstract Altered brain metabolism is associated with progression of Alzheimer’s Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture the tissue organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction visualize mitochondrial structure in from patients mouse models AD. We identified a previously unknown arrest phenotype that results elongated interconnected “mitochondria-on-a-string”...
Dynamin mediates fission of vesicles from the plasma membrane during endocytosis. Typically, dynamin is recruited cytosol to endocytic sites, requiring seconds tens seconds. However, ultrafast endocytosis in neurons internalizes as quickly 50 ms synaptic vesicle recycling. Here, we demonstrate that 1 pre-recruited sites for Specifically, 1xA, a splice variant 1, interacts with Syndapin form molecular condensates on membrane. Single-particle tracking 1xA molecules confirms liquid-like...
CHCHD10-related diseases include mitochondrial DNA instability disorder, frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) clinical spectrum, late-onset spinal motor neuropathy (SMAJ), and Charcot-Marie-Tooth disease type 2 (CMT2). Here, we show that CHCHD10 resides with mitofilin, CHCHD3 CHCHD6 within the "mitochondrial contact site cristae organizing system" (MICOS) complex. mutations lead to MICOS complex disassembly loss of a decrease in nucleoid number disorganization....
Mitochondria shape cytosolic calcium ([Ca2+]c) transients and utilize the mitochondrial Ca2+ ([Ca2+]m) in exchange for bioenergetics output. Conversely, dysregulated [Ca2+]c causes [Ca2+]m overload induces permeability transition pore cell death. Ablation of MCU-mediated uptake exhibited elevated failed to prevent stress-induced The mechanisms these effects remain elusive. Here, we report that mitochondria undergo a Ca2+-induced change is distinct from fission swelling. elevation, but not...
Age-related macular degeneration (AMD), the leading cause of blindness among elderly, is without treatment for early disease. Degenerative retinal pigment epithelial (RPE) cell heterogeneity a well-recognized but understudied pathogenic factor. Due to daily phagocytosis photoreceptor outer segments, unique photo-oxidative stress, and high metabolism maintaining vision, RPE has robust macroautophagy/autophagy, mitochondrial antioxidant networks. However, autophagy subtype, mitophagy, in AMD...
Abstract Compensatory endocytosis keeps the membrane surface area of secretory cells constant following exocytosis. At chemical synapses, clathrin-independent ultrafast maintains such homeostasis. This endocytic pathway is temporally and spatially coupled to exocytosis; it initiates within 50 ms at region immediately next active zone where vesicles fuse. However, coupling mechanism unknown. Here, we demonstrate that filamentous actin organized as a ring, surrounding mouse hippocampal...
Mitochondria are dynamic organelles that constantly fuse and divide to maintain their proper morphology, which is essential for normal functions. Energy production, a central role of mitochondria, demands highly folded structures the mitochondrial inner membrane (MIM) called cristae dimeric phospholipid (PL) cardiolipin (CL). Previous studies identified number factors involved in dynamics, crista formation, CL biosynthesis, yet it still enigmatic how these events interconnected cooperated....
Dynamin-related protein 1 (Drp1) divides mitochondria as a mechano-chemical GTPase. However, the function of Drp1 beyond mitochondrial division is largely unknown. Multiple isoforms are produced through mRNA splicing. One such isoform, Drp1ABCD, contains all four alternative exons and specifically expressed in brain. Here, we studied Drp1ABCD mouse neurons both culture animal systems using isoform-specific knockdown by shRNA knockout CRISPR/Cas9. We found that expression induced during...
Mitochondrial DNA (mtDNA) is packaged into DNA-protein complexes called nucleoids, which are distributed as many small foci in mitochondria. Nucleoids crucial for the biogenesis and function of mtDNA. Here, using a yeast genetic screen components that control nucleoid distribution size, we identify Fcj1 Mos1, two evolutionarily conserved mitochondrial proteins maintain connection between cristae boundary membranes. These also important establishing tubular morphology mitochondria,...
Phosphatidylethanolamine (PE) plays important roles for the structure and function of mitochondria other intracellular organelles. In yeast, majority PE is produced from phosphatidylserine (PS) by a mitochondrion-located PS decarboxylase, Psd1p. Because synthesized in endoplasmic reticulum (ER), transported ER to converted PE. After its synthesis, portion moves back ER. Two mitochondrial proteins located intermembrane space, Ups1p Ups2p, have been shown regulate metabolism controlling export...
Activation of hepatic stellate cells (HSCs) is an integral component the wound-healing process in liver injury/inflammation. However, uncontrolled activation HSCs leads to constant secretion collagen-rich extracellular matrix (ECM) proteins, resulting fibrosis. The enhanced ECM synthesis/secretion demands uninterrupted supply intracellular energy; however, there a paucity data on bioenergetics, particularly mitochondrial (mito) metabolism fibrogenic HSCs. Here, using human and rat vitro, we...
Despite decades of intense study, the molecular basis asynchronous neurotransmitter release remains enigmatic. Synaptotagmin (syt) 7 and Doc2 have both been proposed as Ca 2+ sensors that trigger this mode exocytosis, but conflicting findings led to controversy. Here, we demonstrate at excitatory mouse hippocampal synapses, Doc2α is major sensor for release, while syt7 supports process through activity-dependent docking synaptic vesicles. In synapses lacking Doc2α, after single action...