Pubfacts - Scientific Publication Data
  • Categories
  • |
  • Journals
  • |
  • Authors
  • Login
  • Categories
  • Journals

Search Our Scientific Publications & Authors

Publications
  • Publications
  • Authors
find publications by category +
Translate page:

A novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity.

Authors:
Xin Qi Nir Qvit Yu-Chin Su Daria Mochly-Rosen

J Cell Sci 2013 Feb 13;126(Pt 3):789-802. Epub 2012 Dec 13.

Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Case Western Reserve University School of Medicine Cleveland, OH 44106 Cleveland, OH 44106 USA.

Excessive mitochondrial fission is associated with the pathology of a number of neurodegenerative diseases. Therefore, inhibitors of aberrant mitochondrial fission could provide important research tools in addition to potential leads for drug development. Using a rational approach, we designed a novel and selective peptide inhibitor, P110, of excessive mitochondrial fission. P110 inhibits Drp1 enzyme activity and blocks Drp1/Fis1 interaction in vitro and in cultured neurons, whereas it has no effect on the interaction between Drp1 and other mitochondrial adaptors, as demonstrated by co-immunoprecipitation. Furthermore, using a model of Parkinson's disease (PD) in culture, we demonstrated that P110 is neuroprotective by inhibiting mitochondrial fragmentation and reactive oxygen species (ROS) production and subsequently improving mitochondrial membrane potential and mitochondrial integrity. P110 increased neuronal cell viability by reducing apoptosis and autophagic cell death, and reduced neurite loss of primary dopaminergic neurons in this PD cell culture model. We also found that P110 treatment appears to have minimal effects on mitochondrial fission and cell viability under basal conditions. Finally, P110 required the presence of Drp1 to inhibit mitochondrial fission under oxidative stress conditions. Taken together, our findings suggest that P110, as a selective peptide inhibitor of Drp1, might be useful for the treatment of diseases in which excessive mitochondrial fission and mitochondrial dysfunction occur.

Download full-text PDF

Source
http://dx.doi.org/10.1242/jcs.114439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619809PMC
February 2013

Publication Analysis

Top Keywords

mitochondrial fission
28
excessive mitochondrial
12
mitochondrial
12
aberrant mitochondrial
8
selective peptide
8
peptide inhibitor
8
cell viability
8
p110
7
fission
7
disease culture
4
culture demonstrated
4
reactive oxygen
4
viability basal
4
oxygen species
4
fragmentation reactive
4
demonstrated p110
4
basal conditions
4
mitochondrial fragmentation
4
neuroprotective inhibiting
4
p110 neuroprotective
4

Keyword Occurance

Similar Publications

Surveying keratose sponges (Porifera, Demospongiae, Dictyoceratida) reveals hidden diversity of host specialist barnacles (Crustacea, Cirripedia, Balanidae).

Authors:
Andrew M Hosie Jane Fromont Kylie Munyard Nerida G Wilson Diana S Jones

Mol Phylogenet Evol 2021 Apr 19:107179. Epub 2021 Apr 19.

Collections & Research, Western Australian Museum, 49 Kew St, Welshpool 6106 WA, Australia.

Sponges represent one of the most species-rich hosts for commensal barnacles yet host utilisation and diversity have not been thoroughly examined. This study investigated the diversity and phylogenetic relationships of sponge-inhabiting barnacles within a single, targeted host group, primarily from Western Australian waters. Specimens of the sponge order Dictyoceratida were surveyed and a total of 64 host morphospecies, representing four families, were identified as barnacle hosts during the study. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

Mitochondrial Dynamics for Pollen Development.

Authors:
Masanori Izumi

Plant Physiol 2019 Jun;180(2):686-687

Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai 980-8578, Japan.

View Article and Full-Text PDF
June 2019
Similar Publications

Crystal structure and molecular dynamics of human POLDIP2, a multifaceted adaptor protein in metabolism and genome stability.

Authors:
Anastasija A Kulik Klaudia K Maruszczak Dana C Thomas Naomi L A Nabi Martin Carr Richard J Bingham Christopher D O Cooper

Protein Sci 2021 Apr 21. Epub 2021 Apr 21.

Department of Biological and Geographical Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, West Yorkshire, UK.

Polymerase δ-interacting protein 2 (POLDIP2, PDIP38) is a multifaceted, 'moonlighting' protein, involved in binding protein partners from many different cellular processes, including mitochondrial metabolism and DNA replication and repair. How POLDIP2 interacts with many different proteins is unknown. Towards this goal, we present the crystal structure of POLDIP2 to 2. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

Mitochondrial metabolism as a target for acute myeloid leukemia treatment.

Authors:
Svetlana B Panina Jingqi Pei Natalia V Kirienko

Cancer Metab 2021 Apr 21;9(1):17. Epub 2021 Apr 21.

Department of BioSciences, Rice University, Houston, TX, USA.

Acute myeloid leukemias (AML) are a group of aggressive hematologic malignancies resulting from acquired genetic mutations in hematopoietic stem cells that affect patients of all ages. Despite decades of research, standard chemotherapy still remains ineffective for some AML subtypes and is often inappropriate for older patients or those with comorbidities. Recently, a number of studies have identified unique mitochondrial alterations that lead to metabolic vulnerabilities in AML cells that may present viable treatment targets. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate.

Authors:
Luigi D'Angelo Elisa Astro Monica De Luise Ivana Kurelac Nikkitha Umesh-Ganesh Shujing Ding Ian M Fearnley Giuseppe Gasparre Massimo Zeviani Anna Maria Porcelli Erika Fernandez-Vizarra Luisa Iommarini

Cell Rep 2021 Apr;35(3):109002

Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy. Electronic address:

Complex I (CI) is the largest enzyme of the mitochondrial respiratory chain, and its defects are the main cause of mitochondrial disease. To understand the mechanisms regulating the extremely intricate biogenesis of this fundamental bioenergetic machine, we analyze the structural and functional consequences of the ablation of NDUFS3, a non-catalytic core subunit. We show that, in diverse mammalian cell types, a small amount of functional CI can still be detected in the complete absence of NDUFS3. Read More

View Article and Full-Text PDF
April 2021
Similar Publications
© 2021 PubFacts.
  • About PubFacts
  • Privacy Policy
  • Sitemap