Related Experiment Video

Updated: Jul 7, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

Mitoparan and target-selective chimeric analogues: membrane translocation and intracellular redistribution induces

Sarah Jones1, Cecile Martel, Anne-Sophie Belzacq-Casagrande

  • 1Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK. S.Jones4@wlv.ac.uk

Biochimica Et Biophysica Acta
|February 13, 2008
PubMed

Insights

Mitoparan, a novel peptide, triggers programmed cell death (apoptosis) by targeting mitochondria. This discovery offers potential for new cancer therapies by enhancing apoptosis induction.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Amphipathic peptides like mastoparan can induce cell death through necrosis and apoptosis.
  • Understanding the precise mechanisms of peptide-induced cytotoxicity is crucial for therapeutic development.

Purpose of the Study:

  • To elucidate the specific cytotoxic mechanisms of [Lys(5,8)Aib(10)]mastoparan (mitoparan).
  • To investigate mitoparan's role in inducing apoptosis and its interaction with cellular components.
  • To explore the potential of modified mitoparan peptides as enhanced cytotoxic agents.

Main Methods:

  • Cell-based assays (endonuclease and caspase-3 activation, phosphatidylserine translocation) in U373MG and ECV304 cells.
  • Live cell imaging to track mitoparan localization within cells.
  • Studies on isolated mitochondria to assess permeabilization and cytochrome c release.
  • Synthesis and evaluation of N-terminally acylated chimeric peptides with targeting motifs (RGD, Fas ligand mimetic).

Main Results:

  • Mitoparan specifically induces apoptosis in U373MG and ECV304 cells.
  • Mitoparan translocates to mitochondria after crossing the plasma membrane.
  • Mitoparan causes mitochondrial swelling and permeabilization via VDAC, leading to cytochrome c release.
  • Chimeric mitoparan analogues exhibit enhanced cytotoxic potency.

Conclusions:

  • Mitoparan is a cell-penetrant peptide that induces apoptosis by targeting mitochondria.
  • Mitoparan's mitochondriotoxic and apoptogenic properties are key to its mechanism of action.
  • Modified mitoparan peptides show promise for the study and therapeutic induction of apoptosis.

More Related Videos

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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 precursors...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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,...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.