Related Experiment Video

Updated: Aug 18, 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

Differential susceptibility of subsarcolemmal and intermyofibrillar mitochondria to apoptotic stimuli

Peter J Adhihetty1, Vladimir Ljubicic, Keir J Menzies

  • 1School of Kinesiology and Health Science, York University, Farquharson Building, 302, Toronto, Ontario, Canada M3J 1P3.

American Journal of Physiology. Cell Physiology
|May 20, 2005
PubMed

Insights

Intermyofibrillar (IMF) mitochondria are more susceptible to reactive oxygen species (ROS)-induced apoptosis than subsarcolemmal (SS) mitochondria. This difference is due to IMF mitochondria

Area of Science:

  • Mitochondrial biology
  • Cellular apoptosis
  • Skeletal muscle physiology

Background:

  • Skeletal muscle contains subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial subfractions.
  • Reactive oxygen species (ROS) can trigger apoptosis via mitochondrial release of factors like cytochrome c and apoptosis-inducing factor (AIF).

Purpose of the Study:

  • To compare the apoptotic susceptibility of SS and IMF mitochondria.
  • To elucidate the underlying mechanisms for differential susceptibility to ROS-induced apoptosis.

Main Methods:

  • Investigated protein release from isolated SS and IMF mitochondria upon exposure to hydrogen peroxide (H2O2).
  • Assessed mitochondrial permeability transition pore (mtPTP) opening rates and expression of key components (VDAC, cyclophilin D).
  • Quantified cytochrome c and AIF content, Bax-to-Bcl-2 ratio, ROS production, and membrane potential in both subfractions.

Main Results:

  • IMF mitochondria released significantly more cytochrome c and AIF in response to H2O2 compared to SS mitochondria.
  • IMF mitochondria exhibited higher mtPTP opening rates and greater expression of VDAC and cyclophilin D.
  • SS mitochondria showed a higher Bax-to-Bcl-2 ratio, increased ROS production, and a greater membrane potential.

Conclusions:

  • Divergent protein composition and function of the mtPTP in SS and IMF mitochondria contribute to differential apoptotic factor release.
  • IMF mitochondria are more prone to ROS-induced apoptosis, suggesting their primary role in initiating myonuclear decay and muscle atrophy.

More Related Videos

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor06:26

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor

Published on: April 1, 2011

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

Related Concept Videos

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...
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...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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,...