Synapsin E-domain is essential for α-synuclein function DOI Creative Commons
Alexandra Stavsky, Leonardo A Parra‐Rivas,

Shani Tal

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Aug. 8, 2023

The cytosolic proteins synucleins and synapsins are thought to play cooperative roles in regulating synaptic vesicle (SV) recycling, but mechanistic insight is lacking. Here, we identify the synapsin E-domain as an essential functional binding-partner of α-synuclein (α-syn). Synapsin allows α-syn functionality, binds α-syn, necessary sufficient for enabling effects at synapses cultured mouse hippocampal neurons. Together with previous studies implicating clustering SVs, our experiments advocate a role these two maintaining physiologic SV clusters.

Language: Английский

Plant‐derived peptides for the improvement of Alzheimer's disease: Production, functions, and mechanisms DOI Creative Commons
Like Lin, Cong Li, Tingting Li

et al.

Food Frontiers, Journal Year: 2023, Volume and Issue: 4(2), P. 677 - 699

Published: Feb. 22, 2023

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative with an insidious onset that seriously affects human health. Plant‐derived peptides have been found to hinder the development of AD pathologies, which excellent candidate for preventing AD. However, due excessively complicated pathogenesis and fact most studies on activity plant‐derived are single not deep enough, restricted application AD‐prevention (PADPs). This review summarized currently available means obtaining PADPs, in vitro vivo validation protocols, molecular pathways structure–activity relationship between activity, some perspectives current advanced technologies. paper will help develop foundation production exploitation PADPs.

Language: Английский

Citations

14
Mitochondrial sodium/calcium exchanger (NCLX) regulates basal and starvation‐induced autophagy through calcium signaling DOI
Vitor de Miranda Ramos, Julian D. C. Serna, Eloisa Aparecida Vilas‐Boas

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(3)

Published: Feb. 5, 2024

Mitochondria shape intracellular Ca

Language: Английский

Citations

5
Mild Traumatic Brain Injury Induces Mitochondrial Calcium Overload and Triggers the Upregulation of NCLX in the Hippocampus DOI Creative Commons
Rodrigo G. Mira, Rodrigo A. Quintanilla, Waldo Cerpa

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 403 - 403

Published: Feb. 7, 2023

Traumatic brain injury (TBI) is damage due to external forces. Mild TBI (mTBI) the most common form of TBI, and repeated mTBI a risk factor for developing neurodegenerative diseases. Several mechanisms neuronal have been described in cortex hippocampus, including mitochondrial dysfunction. However, up until now, there no studies evaluating calcium dynamics. Here, we evaluated dynamics an model mice using isolated hippocampal mitochondria biochemical studies. We observed that 24 h after mTBI, decrease membrane potential increase basal matrix levels. These findings are accompanied by increased efflux changes uptake. also NCLX protein levels retention capacity. Our results suggest under cells respond incrementing restore function.

Language: Английский

Citations

11
Mitochondrial redox state, bioenergetics, and calcium transport in caloric restriction: A metabolic nexus DOI
Eloisa Aparecida Vilas‐Boas, Alicia J. Kowaltowski

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 219, P. 195 - 214

Published: April 25, 2024

Language: Английский

Citations

4
TMEM65 regulates NCLX-dependent mitochondrial calcium efflux DOI Creative Commons
Joanne F. Garbincius, Oniel Salik, H Cohen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 9, 2023

Abstract The balance between mitochondrial calcium ( m Ca 2+ ) uptake and efflux regulates ATP production, but if perturbed causes energy starvation or overload cell death. sodium-calcium exchanger, NCLX, is a critical route of in excitable tissues, such as the heart brain, animal models support NCLX promising therapeutic target to limit pathogenic overload. However, mechanisms that regulate activity remain largely unknown. We used proximity biotinylation proteomic screening identify interactome define novel regulators function. Here, we discover inner membrane protein, TMEM65, an NCLX-proximal protein potently enhances sodium (Na + )-dependent efflux. Mechanistically, acute pharmacologic inhibition genetic deletion ablates TMEM65-dependent increase Further, loss-of-function studies show TMEM65 required for Na -dependent Co-fractionation silico structural modeling suggest these two proteins exist common macromolecular complex which directly stimulates In line with findings, knockdown Tmem65 mice promotes skeletal muscle impairs both cardiac neuromuscular further demonstrate excessive permeability transition, whereas overexpression protects against necrotic death during cellular stress. Collectively, our results loss function tissue disrupts NCLX-dependent efflux, causing overload, organ-level dysfunction, gain mitigates effects. These findings essential role regulating modulation strategy control homeostasis.

Language: Английский

Citations

10
The mitochondria as a potential therapeutic target in cerebral I/R injury DOI Creative Commons
Susu Fang, Wenzhou Huang, Xin-Hui Qu

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 7, 2025

Ischemic stroke is a major cause of mortality and disability worldwide. Among patients with ischemic stroke, the primary treatment goal to reduce acute cerebral injury limit infarct size in timely manner by ensuring effective reperfusion through administration either intravenous thrombolysis or endovascular therapy. However, can induce neuronal death, known as injury, for which therapies are lacking. Accumulating data supports paradigm whereby ischemia/reperfusion (I/R) coupled impaired mitochondrial function, contributing pathogenesis stroke. Herein, we review recent evidence demonstrating heterogeneous response following I/R placing specific focus on protein modifications, reactive oxygen species, calcium (Ca2+), inflammation, quality control under experimental conditions using animal models.

Language: Английский

Citations

0
Abnormal levels of mitochondrial Ca 2+ channel proteins in plasma neuron‐derived extracellular vesicles of early schizophrenia DOI
Edward J. Goetzl, Vinod H. Srihari, Maja Mustapić

et al.

The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(8)

Published: July 22, 2022

Structural alterations or quantitative abnormalities of some mitochondrial ion channels and exchangers are associated with altered neuronal functions increased susceptibility to mental illness. Here we have assessed levels functionally prominent calcium channel proteins in plasma neuron-derived extracellular vesicles (NDEVs) living patients first episodes psychosis (FP) matched controls (Cs). NDEVs were enriched an established method precipitation immunoabsorption by anti-human CD171 neural adhesion protein (L1CAM) antibody extracted quantified ELISAs. CD81 exosome marker-normalized NDEV leucine zipper EF-hand containing transmembrane 1 (LETM1), transient receptor potential cation subfamily M, member 4 (TRPM4), solute carrier family 8 B1 (SLC24A6) Na

Language: Английский

Citations

15
Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance DOI Creative Commons
João Victor Cabral‐Costa, Carlos Vicente‐Gutiérrez, Jesús Agulla

et al.

Journal of Neurochemistry, Journal Year: 2022, Volume and Issue: 165(4), P. 521 - 535

Published: Dec. 23, 2022

Intracellular Ca

Language: Английский

Citations

15
Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury DOI Creative Commons
Zhe Liu,

Jingfei Xue,

Canying Liu

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 18(12), P. 2773 - 2780

Published: April 10, 2023

Vision depends on accurate signal conduction from the retina to brain through optic nerve, an important part of central nervous system that consists bundles axons originating retinal ganglion cells. The mammalian system, cannot regenerate once it is injured, leading permanent vision loss. To date, there no clinical treatment can nerve and restore vision. Our previous study found mobile zinc (Zn2+) level increased rapidly after injury in retina, specifically vesicles inner plexiform layer. Furthermore, chelating Zn2+ significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out transporter 3 (ZnT3) amacrine cells or construct two transgenic mouse lines (VGATCreZnT3fl/fl VGLUT2CreZnT3fl/fl, respectively). We obtained direct evidence response was also selective deletion ZnT3 cell survival crush injury, improved function, recovery. Sequencing analysis reginal revealed inhibiting release presynaptic affected transcription key genes related postsynaptic neurons, regulated synaptic connection between cells, fate These results suggest trigger transcriptomic changes neuronal growth thereby influencing plasticity networks. make theory zinc-dependent death more complete provide new insights into complex interactions

Language: Английский

Citations

9
Post-translational modifications and protein quality control of mitochondrial channels and transporters DOI Creative Commons
Ashlesha Kadam, Pooja Jadiya, Dhanendra Tomar

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 3, 2023

Mitochondria play a critical role in energy metabolism and signal transduction, which is tightly regulated by proteins, metabolites, ion fluxes. Metabolites homeostasis are mainly mediated channels transporters present on mitochondrial membranes. comprise two distinct compartments, the outer membrane (OMM) inner (IMM), have differing permeabilities to ions metabolites. The OMM semipermeable due presence of non-selective molecular pores, while IMM highly selective impermeable specialized regulate metabolite These modulated various post-translational modifications (PTMs), including phosphorylation, oxidative modifications, ions, metabolites binding, glycosylation, acetylation, others. Additionally, protein quality control (MPQC) system plays crucial ensuring efficient flux through membranes selectively removing mistargeted or defective proteins. Inefficient functioning mitochondria can disrupt cellular homeostasis, leading onset pathological conditions. In this review, we provide comprehensive overview current understanding terms their functions, PTMs, mechanisms.

Language: Английский

Citations

8