Related Experiment Video

Updated: Aug 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

Role of nitric oxide-induced mtDNA damage in mitochondrial dysfunction and apoptosis

Lyudmila I Rachek1, Valentina I Grishko, Susan P Ledoux

  • 1Department of Cell Biology and Neuroscience, College of Medicine, University of South Alabama, Mobile, 36688, USA.

Free Radical Biology & Medicine
|March 8, 2006
PubMed

Insights

Enhanced mitochondrial DNA repair using hOGG1 protects cells from nitric oxide (NO) toxicity. This study shows improved cell survival and reduced apoptosis when mitochondrial DNA repair is augmented, highlighting a novel protective strategy against NO-induced damage.

Area of Science:

  • Mitochondrial biology
  • DNA repair mechanisms
  • Cellular toxicology

Background:

  • Nitric oxide (NO) is cytotoxic, genotoxic, and preferentially damages mitochondrial DNA (mtDNA).
  • The DNA repair protein hOGG1, when targeted to mitochondria, enhances mtDNA repair and cellular survival.
  • The protective potential of augmented mitochondrial hOGG1 against NO-induced damage remains to be fully elucidated.

Purpose of the Study:

  • To investigate whether enhanced mitochondrial DNA repair via conditional expression of hOGG1 protects cells from nitric oxide (NO)-induced damage.
  • To evaluate the impact of augmented hOGG1 on NO-induced mtDNA damage, ATP production, and apoptosis.

Main Methods:

  • Utilized HeLa TetOff/MTS-OGG1-transfected cells for conditional mitochondrial expression of hOGG1.
  • Exposed cells to NO generated from PAPA NONOate in the presence or absence of doxycycline (Dox).
  • Assessed mtDNA repair efficiency, cellular survival, ATP production, and apoptosis.

Main Results:

  • Cells expressing mitochondrial hOGG1 demonstrated enhanced repair of NO-induced mtDNA damage.
  • Increased cellular survival was observed in cells with augmented mitochondrial hOGG1 following NO exposure.
  • Conditional hOGG1 expression reduced NO-induced inhibition of ATP production and protected against apoptosis.

Conclusions:

  • Augmented mitochondrial expression of hOGG1 enhances the repair of nitric oxide-induced mitochondrial DNA damage.
  • Mitochondrial targeting of hOGG1 confers significant cellular protection against NO toxicity, including improved survival and prevention of apoptosis.
  • This strategy offers a promising approach to mitigate the deleterious effects of NO on cellular function and integrity.

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

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

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,...
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...
Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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.