A5071272167- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Autophagy in Disease and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Photoreceptor and optogenetics research
- Sirtuins and Resveratrol in Medicine
- Adipose Tissue and Metabolism
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- bioluminescence and chemiluminescence research
- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Pancreatic function and diabetes
- Neurological disorders and treatments
- Cell Image Analysis Techniques
- Genomics, phytochemicals, and oxidative stress
- Machine Learning in Bioinformatics
- Axon Guidance and Neuronal Signaling
- Ion channel regulation and function
- Biomedical Text Mining and Ontologies
- Bioinformatics and Genomic Networks
- Physiological and biochemical adaptations
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Nerve injury and regeneration
Washington University in St. Louis
2021-2024
Center for Neuro-Oncology
2022-2024
Harvard University
2011-2022
Boston Children's Hospital
2011-2022
Weill Cornell Medicine
2017-2019
Cornell University
2017-2019
University of Alberta
2015
To minimize oxidative damage to the cell, malfunctioning mitochondria need be removed by mitophagy. In neuronal axons, mitochondrial may occur in distal regions, far from soma where most lysosomal degradation is thought occur. this paper, we report that PINK1 and Parkin, two Parkinson’s disease–associated proteins, mediate local mitophagy of dysfunctional axons. reduce cytotoxicity mimic physiological levels damage, selectively damaged a subset hippocampal Parkin was rapidly recruited axons...
Glucose has long been considered a primary energy source for synaptic function. However, it remains unclear to what extent alternative fuels, such as lactate/pyruvate, contribute powering transmission. By detecting individual release events in hippocampal synapses, we find that mitochondrial ATP production regulates basal vesicle probability and location within the active zone (AZ), evoked by single action potentials. Mitochondrial inhibition shifts closer AZ center alters efficiency of...
Mutations in the PINK1 and PARK2/PARKIN genes are associated with hereditary early onset Parkinson disease (PD), cell lines corresponding gene products play a critical role mitophagic clearance of damaged mitochondria. In neurons, however, where extraordinary cellular shapes pose particular challenges for maintaining healthy mitochondria, pathways mitophagy less well understood. Both location at which occurs involvement PARK2 have been controversial. Here we review our recent study found...
ABSTRACT Glucose has long been considered the primary fuel source for brain. However, glucose levels fluctuate in brain during sleep, intense circuit activity, or dietary restrictions, posing significant metabolic stress. Here, we demonstrate that mammalian utilizes pyruvate as a source, and can support neuronal viability absence of glucose. Nerve terminals are sites vulnerability within neuron show mitochondrial uptake is critical step oxidative ATP production hippocampal terminals. We find...
Neurotransmission is an energetically expensive process that underlies cognition. During intense electrical activity or dietary restrictions, the glucose level in brain plummets, forcing neurons to utilize alternative fuels. However, molecular mechanisms of neuronal metabolic plasticity remain poorly understood. Here, we demonstrate glucose-deprived activate CREB and PGC1α transcriptional program, which induces expression mitochondrial deacetylase Sirtuin 3 (Sirt3) both vitro vivo. We show...
Glucose has long been considered the primary fuel source for brain. However, glucose levels fluctuate in brain during sleep or circuit activity, posing major metabolic stress. Here, we demonstrate that mammalian uses pyruvate as a source, and can support neuronal viability absence of glucose. Nerve terminals are sites vulnerability, show mitochondrial uptake is critical step oxidative ATP production hippocampal terminals. We find carrier post-translationally modified by lysine acetylation,...
The nuclear factor erythroid 2-related 2 (NRF2) transcription activates cytoprotective and metabolic gene expression in response to various electrophilic stressors. Constitutive NRF2 activity promotes cancer progression, whereas decreased function contributes neurodegenerative diseases. We used proximity proteomic analysis define protein networks for its family members NRF1, NRF3, the heterodimer MAFG. A functional screen of co-complexed proteins revealed previously uncharacterized...
Significance: The firefly enzyme luciferase has been used in a wide range of biological assays, including bioluminescence imaging adenosine triphosphate (ATP). biosensor Syn-ATP utilizes subcellular targeting to nerve terminals for optical measurement ATP this compartment. Manual analysis signals is challenging due signal heterogeneity and cellular motion long sessions. Here, we have leveraged machine learning tools develop method images. Aim: Our goal was create semiautomated pipeline...
SUMMARY Glucose has long been considered a primary source of energy for synaptic function. However, it remains unclear under what conditions alternative fuels, such as lactate/pyruvate, contribute to powering transmission. By detecting individual release events in cultured hippocampal synapses, we found that mitochondrial ATP production from oxidation lactate/pyruvate regulates basal vesicle probability and location within the active zone (AZ) evoked by single action potentials (APs)....
Abstract PTEN-induced kinase 1 (PINK1) is a very short-lived protein that required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because short half-life PINK1 limits its ability to be trafficked into neurites, local translation this mitophagy pathway active far from soma. The Pink1 transcript associated with cotransported neuronal mitochondria. In concert translation, mitochondrial outer membrane Synaptojanin 2 binding (SYNJ2BP) (SYNJ2) are tethering...
Neurotransmission is an energetically expensive process that underlies cognition. During intense electrical activity or dietary restrictions, glucose levels in the brain plummet, forcing neurons to utilize alternative fuels. However, molecular mechanisms of neuronal metabolic plasticity remain poorly understood. Here, we demonstrate glucose-deprived activate CREB and PGC1α transcriptional program induces expression mitochondrial deacetylase Sirtuin 3 (Sirt3) both
The brain is a vulnerable metabolic organ and must adapt to different fuel conditions sustain function. Nerve terminals are locus of this vulnerability but how they regulate ATP synthesis as vary unknown. We show that synapses can switch from glycolytic oxidative metabolism, do so, rely on activity-driven presynaptic mitochondrial Ca2+ uptake accelerate production. demonstrate while in non-neuronal cells requires elevated extramitochondrial Ca2+, axonal mitochondria readily take up response...
Abstract Significance The firefly enzyme luciferase has been used in a wide range of biological assays, including bioluminescence imaging ATP. biosensor Syn-ATP utilizes subcellular targeting to nerve terminals for optical measurement ATP this compartment. Manual analysis signals is challenging due signal heterogeneity and cellular motion long sessions. Here, we have leveraged machine learning tools develop method images. Aim Our goal was create semi-automated pipeline improve measurements...