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

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

18.4K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
18.4K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

11.9K
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,...
11.9K
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

4.5K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
4.5K
Mitochondrial Membranes01:45

Mitochondrial Membranes

16.6K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
16.6K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

3.5K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
3.5K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

5.6K
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...
5.6K

You might also read

Related Articles

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

Sort by
Same author

Improving hepatic metabolic function with 3D iPSC-derived human hepatocytes.

Cell biology and toxicology·2026
Same author

RYR:ATP6V0A1 complexes couple ER-lysosome contact sites to dynamic autophagy control.

Autophagy·2026
Same author

Pharmacological and Biological Tools to Inhibit IP<sub>3</sub> Receptors.

Cold Spring Harbor perspectives in biology·2026
Same author

Organobodies: a robust and size-controllable system for generating scalable hiPSC-derived liver organoids for drug toxicity screening.

Biofabrication·2026
Same author

Functional and structural basis of a hypermorphic TRPC3 variant.

Science advances·2026
Same author

Anti-apoptotic BCL-2 binds to all three IP3R isoforms, thereby limiting the Ca2+-flux properties of IP3R homo-tetramers.

Open biology·2026

Related Experiment Video

Updated: Jan 10, 2026

Author Spotlight: Decoding Mitochondrial Aging
08:48

Author Spotlight: Decoding Mitochondrial Aging

Published on: June 30, 2023

4.7K

CISD2 ensures adequate ER-mitochondrial coupling, critically supporting mitochondrial function in neurons.

Jens Loncke1, Ian de Ridder1, Rita La Rovere1

  • 1Laboratory for Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Campus Gasthuisberg O/N-1 B-802, Herestraat 49, 3000, Leuven, Belgium.

Acta Neuropathologica Communications
|November 27, 2025
PubMed
Summary

Loss of Cisd2 protein impairs calcium (Ca2+) transfer between cellular compartments, particularly affecting neuronal function and resilience in Wolfram syndrome type 2 (WS2). This highlights Cisd2

Keywords:
ApoptosisCa2+ signalingCisd2ER-mitochondria contact sitesNeurodegenerationWolfram syndrome

More Related Videos

Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers
10:31

Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers

Published on: September 29, 2017

10.6K
Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry
08:19

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry

Published on: May 5, 2022

2.8K

Related Experiment Videos

Last Updated: Jan 10, 2026

Author Spotlight: Decoding Mitochondrial Aging
08:48

Author Spotlight: Decoding Mitochondrial Aging

Published on: June 30, 2023

4.7K
Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers
10:31

Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers

Published on: September 29, 2017

10.6K
Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry
08:19

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry

Published on: May 5, 2022

2.8K

Area of Science:

  • Cell Biology
  • Neuroscience
  • Mitochondrial Biology

Background:

  • Cisd2, an iron-sulfur cluster transfer protein, is crucial for cellular homeostasis.
  • Loss of Cisd2 causes Wolfram syndrome type 2 (WS2), impacting pancreatic beta cells and neurons.
  • Cisd2's role in intracellular calcium (Ca2+) signaling and ER-mitochondria communication is not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Cisd2 regulates intracellular Ca2+ dynamics.
  • To investigate the cellular consequences of Cisd2 deficiency on ER-mitochondria tethering and Ca2+ transfer.
  • To assess the impact of Cisd2 loss on neuronal function, mitochondrial health, and stress resilience in WS2-relevant models.

Main Methods:

  • Utilized HeLa cells and human induced pluripotent stem cell-derived cortical neurons.
  • Investigated Cisd2 interactions with inositol-1,4,5-trisphosphate receptors.
  • Assessed ER-mitochondria tethering, Ca2+ signaling, mitochondrial function, and autophagic flux.
  • Evaluated neuronal sensitivity to apoptosis-inducing agents like staurosporine.

Main Results:

  • Cisd2 deficiency reduced ER-mitochondrial Ca2+ transfer in HeLa cells.
  • In cortical neurons, Cisd2 loss severely impaired glutamate-evoked Ca2+ responses and mitochondrial Ca2+ uptake.
  • Cisd2-deficient neurons exhibited declined mitochondrial function and increased sensitivity to apoptosis.
  • Autophagic flux was promoted in both cell types upon Cisd2 deficiency.

Conclusions:

  • Cisd2 plays a critical role in regulating ER-mitochondria Ca2+ handling and tethering.
  • Neuronal health and stress resilience are highly dependent on Cisd2 for maintaining mitochondrial function.
  • This study provides insights into the cellular basis of WS2 and identifies Cisd2 as a key factor in neuronal survival.