Related Experiment Video

Updated: Sep 28, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Up-regulation of c-Jun N-terminal kinase pathway in Friedreich's ataxia cells

Luigi Pianese1, Luca Busino, Irene De Biase

  • 1BioGeM Consortium and Department of Molecular and Cellular Biology and Pathology and IEOS, CNR, Federico II University, Naples, Italy. pianese@biogem.it

Human Molecular Genetics
|October 24, 2002
PubMed

Insights

Friedreich ataxia (FRDA) involves low frataxin, leading to oxidative stress. FRDA cells show a hyperactive stress pathway, with increased caspase-9 activation, contributing to the disease.

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Friedreich ataxia (FRDA) is a severe hereditary ataxia caused by reduced mitochondrial frataxin.
  • Oxidative stress is increasingly implicated in FRDA pathogenesis.
  • Understanding cellular stress responses in FRDA is crucial.

Purpose of the Study:

  • To investigate the stress signaling pathway in a cellular model of frataxin deficiency.
  • To examine the role of stress kinases and caspases in FRDA fibroblasts.
  • To elucidate the contribution of cellular stress to FRDA pathology.

Main Methods:

  • Generated an in vitro cellular model of regulated human frataxin overexpression.
  • Utilized differential display to identify gene expression changes.
  • Studied stress kinases (JNK pathway) and caspase activation in FRDA and control fibroblasts.

Main Results:

  • Frataxin overexpression led to downregulation of mitogen activated protein kinase kinase 4.
  • FRDA fibroblasts exhibited upregulated phospho-JNK and phospho-c-Jun upon environmental stress.
  • Significantly higher caspase-9 activation was observed in FRDA fibroblasts after serum withdrawal.

Conclusions:

  • FRDA patient cells display a hyperactive stress signaling pathway.
  • This hyperactivity, involving stress kinases and caspases, may contribute to FRDA pathogenesis.
  • Frataxin's role in FRDA may be partly explained by its influence on cellular stress responses.

More Related Videos

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...