Damage targeted to the mitochondrial interior induces autophagy, cell cycle arrest and, only at high doses, apoptosis

Ausra Sasnauskiene1, Jurgis Kadziauskas, Neringa Vezelyte

  • 1Vilnius University, Vilnius, Lithuania.

Autophagy
|July 3, 2009
PubMed

Insights

Photodynamic treatment targeting the mitochondrial interior in A431 cells induced apoptosis at high doses. Lower doses caused cell cycle inhibition and autophagy, not cell death.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Apoptosis Research

Background:

  • Outer mitochondrial membrane permeabilization is key to apoptosis.
  • Cellular response to inner mitochondrial damage is less understood.

Purpose of the Study:

  • Investigate cellular responses to damage within the mitochondrial interior.
  • Determine the role of reactive oxygen species (ROS) in the mitochondrial inner space.

Main Methods:

  • Utilized photodynamic treatment (PDT) with Safranin O (Safr) to generate singlet oxygen in mitochondria.
  • Applied PDT to epidermoid carcinoma A431 cells.
  • Assessed cell morphology, viability, cell cycle, and apoptosis markers.

Main Results:

  • Low-to-intermediate Safr-PDT doses (up to CD50) inhibited cell cycle and enhanced autophagy without inducing cell death.
  • High Safr-PDT doses (beyond CD70) triggered apoptosis, evidenced by cytochrome c release and caspase-3 activation.
  • Autophagy was enhanced across tested Safr-PDT doses.

Conclusions:

  • Damage to the mitochondrial interior can induce apoptosis via outer membrane permeabilization at sufficient levels.
  • Cellular response to inner mitochondrial damage is dose-dependent, involving cell cycle arrest, autophagy, and apoptosis.
  • Safranin O-mediated PDT is a viable tool for studying mitochondrial-targeted damage and apoptosis induction.

Related Concept Videos

Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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...
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,...
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.