Related Experiment Video

Updated: Sep 11, 2026

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
09:27

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

A structural view of mitochondria-mediated apoptosis

Y Shi1

  • 1Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA. yshi@molbio.princeton.edu

Nature Structural Biology
|April 27, 2001
PubMed

Insights

Mitochondria-mediated apoptosis is crucial for development and homeostasis, but its dysregulation leads to cancer. Released mitochondrial proteins like cytochrome c activate caspases, driving programmed cell death through a conserved mechanism.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Mitochondria-mediated apoptosis is vital for animal development and tissue homeostasis.
  • Dysregulation of this process is linked to malignant disorders, notably cancer.
  • Key mitochondrial proteins, cytochrome c and Smac/DIABLO, are released during apoptosis.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying mitochondria-mediated apoptosis.
  • To understand the synergistic activation of caspases by released mitochondrial proteins.
  • To identify the conserved evolutionary basis of apoptosis from invertebrates to mammals.

Main Methods:

  • Biochemical assays to study protein interactions and functions.
  • Structural biology techniques to determine the atomic resolution of key complexes.
  • Comparative analysis across different species to establish evolutionary conservation.

Main Results:

  • Cytochrome c and Smac/DIABLO synergistically activate caspases in the cytosol.
  • These proteins activate Apaf-1 and overcome Inhibitors of Apoptosis Proteins (IAPs).
  • A conserved molecular mechanism for apoptosis was identified across diverse animal species.

Conclusions:

  • Mitochondria-mediated apoptosis involves a conserved, synergistic caspase activation pathway.
  • Understanding this pathway provides insights into cancer development and potential therapeutic targets.
  • The findings highlight the fundamental role of programmed cell death in multicellular organisms.

More Related Videos

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome07:56

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

Published on: November 30, 2022

Related Concept Videos

Mitochondrial Membranes01:45

Mitochondrial Membranes

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,...
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,...
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.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
Mitochondrial Membranes01:45

Mitochondrial Membranes

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,...