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Updated: Apr 21, 2026

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl

Published on: November 28, 2014

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Granzyme B-induced mitochondrial ROS are required for apoptosis

G Jacquemin1, D Margiotta1, A Kasahara1

  • 1CMU, Cell Physiology and Metabolism, Faculté de Médecine, Université de Genève, Geneva, Switzerland.

Cell Death and Differentiation
|November 1, 2014
PubMed

Insights

Granzyme B (GB) triggers cell death by directly damaging mitochondria, causing reactive oxygen species (ROS) production. This ROS generation is crucial for apoptosis, DNA fragmentation, and cell death.

Area of Science:

  • Cell Biology
  • Immunology
  • Biochemistry

Background:

  • Caspases and granzyme B (GB) are known to induce apoptosis, involving reactive oxygen species (ROS) and mitochondrial damage.
  • The precise mechanisms by which GB induces ROS and its necessity in GB-mediated apoptosis remain unclear.

Purpose of the Study:

  • To elucidate the role of ROS in GB-mediated apoptosis.
  • To investigate the mechanism by which GB induces ROS production.

Main Methods:

  • Investigated GB-induced cell death in the presence and absence of ROS scavengers.
  • Analyzed mitochondrial integrity and function via assays for transmembrane potential, outer membrane permeabilization (MOMP), and respiratory chain activity.
  • Examined the direct effect of GB on mitochondrial complexes, specifically Complex I subunits (NDUFV1, NDUFS1, NDUFS2).

Main Results:

  • GB induces cell death in an ROS-dependent manner, independent of caspases and MOMP.
  • GB directly cleaves mitochondrial Complex I subunits (NDUFV1, NDUFS1, NDUFS2), leading to ROS production within mitochondria (mitocentric ROS).
  • GB-induced mitocentric ROS are essential for efficient apoptogenic factor release, DNA fragmentation, and lysosomal rupture, with ROS scavenging delaying these processes.

Conclusions:

  • Granzyme B triggers apoptosis through a ROS-dependent pathway initiated by direct mitochondrial damage.
  • Targeting mitochondrial Complex I is a key mechanism for GB-induced ROS production, promoting various hallmarks of cell death.
  • ROS play a significant, pro-apoptotic role in granzyme B-mediated cytotoxicity.

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