Heterogeneous Expression of Nuclear Encoded Mitochondrial Genes Distinguishes Inhibitory and Excitatory Neurons DOI Creative Commons
Meghan E. Wynne, Alicia R. Lane, Kaela S. Singleton

et al.

eNeuro, Journal Year: 2021, Volume and Issue: 8(4), P. ENEURO.0232 - 21.2021

Published: July 1, 2021

Mitochondrial composition varies by organ and their constituent cell types. This mitochondrial diversity likely determines variations in function. However, the heterogeneity of mitochondria brain remains underexplored despite large types neuronal tissue. Here, we used molecular systems biology tools to address whether region type mice. We reasoned that proteomics transcriptomics microdissected regions combined with analysis single-cell mRNA sequencing (scRNAseq) could reveal extent compositional diversity. selected nuclear encoded gene products forming complexes fixed stoichiometry, such as respiratory chain ribosome, well molecules perform function monomers, family SLC25 transporters. found proteome encompassing these nuclear-encoded genes obtained from tissue segregated hippocampus, striatum, cortex each other. Nuclear-encoded transcripts only segregate when was performed at level. In fact, transcriptomes were able distinguish glutamatergic distinct GABAergic neurons one another. Within categories, unique SLC25A transporters identify subpopulations. Our results demonstrate heterogeneous across postulate influences regional type-specific mechanisms health disease.

Language: Английский

Immunometabolism in the Brain: How Metabolism Shapes Microglial Function DOI
Louis‐Philippe Bernier, Elisa M. York, Brian A. MacVicar

et al.

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 43(11), P. 854 - 869

Published: Sept. 18, 2020

Language: Английский

Citations

184
The metabolic basis of epilepsy DOI
Jong M. Rho, Detlev Boison

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(6), P. 333 - 347

Published: March 31, 2022

Language: Английский

Citations

156
Principles and functions of metabolic compartmentalization DOI
Liron Bar‐Peled, Nora Kory

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(10), P. 1232 - 1244

Published: Oct. 20, 2022

Language: Английский

Citations

81
Organelle transporters and inter-organelle communication as drivers of metabolic regulation and cellular homeostasis DOI Creative Commons
Aakriti Jain, Roberto Zoncu

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 60, P. 101481 - 101481

Published: March 25, 2022

Spatial compartmentalization of metabolic pathways within membrane-separated organelles is key to the ability eukaryotic cells precisely regulate their biochemical functions. Membrane-bound such as mitochondria, endoplasmic reticulum (ER) and lysosomes enable concentration precursors optimized chemical environments, greatly accelerating efficiency both anabolic catabolic reactions, enabling division labor optimal utilization resources. However, also poses a challenge because it creates spatial discontinuities that must be bridged for reaction cascades connected completed. To do so, employ different methods coordinate fluxes occurring in organelles, membrane-localized transporters facilitate regulated metabolite exchange between mitochondria lysosomes, non-vesicular transport via physical contact sites connecting ER with well localized regulatory signaling processes coordinately activity all these organelles.

Language: Английский

Citations

75
Absolute measurement of fast and slow neuronal signals with fluorescence lifetime photometry at high temporal resolution DOI Creative Commons

Bart Lodder,

Tarun V. Kamath,

Ecaterina Savenco

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

The concentrations of extracellular and intracellular signaling molecules, such as dopamine cAMP, change over both fast slow timescales impact downstream pathways in a cell-type specific manner. Fluorescence sensors currently used to monitor signals vivo are typically optimized detect fast, relative changes concentration the target molecule. They less well suited slowly-changing rarely provide absolute measurements either components. Here, we developed system for fluorescence lifetime photometry at high temporal resolution (FLIPR) that utilizes frequency-domain analog processing measure genetically-encoded speed but with long-term stability picosecond precision freely moving mice. We applied FLIPR investigate two functionally distinct regions striatum, nucleus accumbens core (NAC) tail striatum (TOS). observed higher tonic levels baseline TOS compared NAC detected differential dynamic responses phasic appetitive aversive stimuli. Thus, enables simple monitoring time-scale neuronal units, revealing previously unappreciated spatial variation even well-studied systems.

Language: Английский

Citations

3
A high-throughput multiparameter screen for accelerated development and optimization of soluble genetically encoded fluorescent biosensors DOI Creative Commons
Dorothy Koveal, Paul C. Rosen, Dylan J. Meyer

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 25, 2022

Genetically encoded fluorescent biosensors are powerful tools used to track chemical processes in intact biological systems. However, the development and optimization of remains a challenging labor-intensive process, primarily due technical limitations methods for screening candidate biosensors. Here we describe modality that combines droplet microfluidics automated fluorescence imaging provide an order magnitude increase throughput. Moreover, unlike current techniques limited single biosensor feature at time (e.g. brightness), our method enables evaluation multiple features contrast, affinity, specificity) parallel. Because can covary, this capability is essential rapid optimization. We use system generate high-performance lactate be quantify intracellular concentrations. This biosensor, named LiLac, constitutes significant advance metabolite sensing demonstrates power approach.

Language: Английский

Citations

70
Ketone Bodies in the Brain Beyond Fuel Metabolism: From Excitability to Gene Expression and Cell Signaling DOI Creative Commons
Darío García-Rodríguez, Alfredo Giménez-Cassina

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: Aug. 27, 2021

Ketone bodies are metabolites that replace glucose as the main fuel of brain in situations scarcity, including prolonged fasting, extenuating exercise, or pathological conditions such diabetes. Beyond their role an alternative for brain, impact ketone on neuronal physiology has been highlighted by use so-called “ketogenic diets,” which were proposed about a century ago to treat infantile seizures. These diets mimic fasting reducing drastically intake carbohydrates and proteins replacing them with fat, thus promoting ketogenesis. The fact ketogenic have profound effect epileptic seizures points complex biological effects addition source ATP. In this review, we specifically focus ability regulate excitability gene expression respond oxidative stress. Finally, also discuss capacity signaling molecules cells.

Language: Английский

Citations

66
Calculation of ATP production rates using the Seahorse XF Analyzer DOI Creative Commons
Brandon R. Desousa, Kristen K.O. Kim, Anthony E. Jones

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(10)

Published: Aug. 7, 2023

Abstract Oxidative phosphorylation and glycolysis are the dominant ATP‐generating pathways in mammalian metabolism. The balance between these two is often shifted to execute cell‐specific functions response stimuli that promote activation, proliferation, or differentiation. However, measurement of metabolic switches has remained mostly qualitative, making it difficult discriminate healthy, physiological changes energy transduction compensatory responses due dysfunction. We therefore present a broadly applicable method calculate ATP production rates from oxidative using Seahorse XF Analyzer data empirical conversion factors. quantify bioenergetic observed during macrophage polarization as well cancer cell adaptation vitro culture conditions. Additionally, we detect substantive utilization upon neuronal depolarization T receptor activation not evident steady‐state measurements. This generates single readout allows direct comparison produced live cells. manuscript provides framework for tailoring calculations specific systems experimental

Language: Английский

Citations

35
More than double the fun with two-photon excitation microscopy DOI Creative Commons
Peter Luu, Scott E. Fraser, Falk Schneider

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 26, 2024

Abstract For generations researchers have been observing the dynamic processes of life through lens a microscope. This has offered tremendous insights into biological phenomena that span multiple orders time- and length-scales ranging from pure magic molecular reorganization at membrane immune cells, to cell migration differentiation during development or wound healing. Standard fluorescence microscopy techniques offer glimpses such in vitro, however, when applied intact systems, they are challenged by reduced signal strengths signal-to-noise ratios result deeper imaging. As remedy, two-photon excitation (TPE) takes special place, because it allows us investigate vivo, their natural environment, even living animal. Here, we review fundamental principles underlying TPE aimed basic advanced users interested adopting for intravital We focus on applications neurobiology, present current trends towards faster, wider imaging, discuss combination with photon counting technologies metabolic imaging spectroscopy, as well highlight outstanding issues drawbacks application these methodologies.

Language: Английский

Citations

17
Fast and slow: Recording neuromodulator dynamics across both transient and chronic time scales DOI Creative Commons
Pingchuan Ma, Peter Chen, Elizabeth I. Tilden

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(8)

Published: Feb. 21, 2024

Neuromodulators transform animal behaviors. Recent research has demonstrated the importance of both sustained and transient change in neuromodulators, likely due to tonic phasic neuromodulator release. However, no method could simultaneously record types dynamics. Fluorescence lifetime optical reporters offer a solution because it allows high temporal resolution is impervious sensor expression differences across chronic periods. Nevertheless, fluorescence entire classes sensors was previously known. Unexpectedly, we find that several intensity-based also exhibit responses. Furthermore, show measures vivo dynamics with consistency animals time. Thus, report can measure over time scales, promising reveal roles multi-time scale diseases, response therapies, development aging.

Language: Английский

Citations

11