Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

15.7K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
15.7K
ATP Synthase: Structure01:18

ATP Synthase: Structure

14.0K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
14.0K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

9.8K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
9.8K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

2.9K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.9K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

5.1K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
5.1K
Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

6.8K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
6.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

ATP13A2 Loss of Function-Driven Polyamine Dysregulation Induces SAM Depletion and Epigenetic Astrocyte Toxicity.

bioRxiv : the preprint server for biology·2026
Same author

Generation and characterization of human induced pluripotent stem cells from neuropathologically confirmed multiple system atrophy patient-derived fibroblasts.

Frontiers in immunology·2026
Same author

Opposing Roles for ATP13A2 and ATP13A3 in Breast Cancer Subtype-Specific Polyamine Homeostasis.

Biomolecules·2026
Same author

Immune cells from the gut drive development of Parkinson's disease in the brain.

Nature·2026
Same author

Absence of Ledgf in mouse brain affects the Kmt2a/b and polycomb balance, synaptic transmission and motor function.

Acta neuropathologica communications·2026
Same author

Inactive ryanodine receptors sustain lysosomal availability for autophagy by promoting ER-lysosomal contact site formation.

Nature communications·2026

Related Experiment Video

Updated: Nov 10, 2025

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
07:56

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time

Published on: May 30, 2021

3.4K

ATP13A2 Regulates Cellular α-Synuclein Multimerization, Membrane Association, and Externalization.

Jianmin Si1, Chris Van den Haute1,2, Evy Lobbestael1

  • 1Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Herestraat 49, Bus 1023, 3000 Leuven, Belgium.

International Journal of Molecular Sciences
|April 3, 2021
PubMed
Summary
This summary is machine-generated.

The ATP13A2 transporter impacts neurodegenerative diseases by affecting α-synuclein. Loss of ATP13A2 causes α-synuclein multimerization, while its overexpression protects against it, revealing dual roles in polyamine transport and α-synuclein regulation.

Keywords:
ATP13A2Parkinson’s diseasespermineα-synucleinα-synuclein multimerization

More Related Videos

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
09:36

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays

Published on: August 13, 2017

6.9K
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
15:04

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

6.1K

Related Experiment Videos

Last Updated: Nov 10, 2025

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
07:56

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time

Published on: May 30, 2021

3.4K
Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
09:36

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays

Published on: August 13, 2017

6.9K
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
15:04

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

6.1K

Area of Science:

  • Neurobiology
  • Cell Biology
  • Molecular Medicine

Background:

  • ATP13A2 is a lysosomal transporter linked to neurodegenerative diseases like Parkinson's.
  • Mutations in ATP13A2 impair polyamine export, causing lysosomal dysfunction.
  • ATP13A2's role in α-synuclein regulation remains unclear.

Purpose of the Study:

  • To investigate the mechanisms linking ATP13A2 activity to α-synuclein behavior.
  • To explore ATP13A2's function in cell models with altered transporter activity.

Main Methods:

  • Utilized cell models with modified ATP13A2 expression (loss-of-function and overexpression).
  • Assessed lysosomal integrity, α-synuclein multimerization, and membrane association.
  • Investigated α-synuclein secretion via nanovesicles and polyubiquitination.

Main Results:

  • Loss of ATP13A2 impairs lysosomal integrity and promotes α-synuclein multimerization, exacerbated by stress or spermine.
  • ATP13A2 overexpression protects against α-synuclein multimerization and enhances its secretion via nanovesicles.
  • ATP13A2 influences α-synuclein polyubiquitination and externalization through both transport-dependent and independent mechanisms.

Conclusions:

  • ATP13A2 plays a critical role in maintaining lysosomal function and regulating α-synuclein.
  • The transporter impacts α-synuclein multimerization, secretion, and ubiquitination.
  • ATP13A2's functions extend beyond its ATPase and transport activity, influencing neurodegeneration pathways.