Mitochondrial DNA depletion causes decreased ROS production and resistance to apoptosis

Hulin Chen1, Junling Wang2, Zhongrong Liu1

  • 1Department of Dermatology, Guangzhou General Hospital of Guangzhou Military Command (Liuhuaqiao Hospital), Guangzhou, Guangdong 510010, P.R. China.

Insights

Mitochondrial DNA-depleted cells show increased resistance to ultraviolet radiation-induced apoptosis. This resistance in Rho˚206 cells is linked to reduced reactive oxygen species production compared to parental 143B cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial DNA (mtDNA) depletion is common in various diseases, including cancer.
  • Understanding the role of mtDNA in cellular responses to stress is crucial for disease research.

Purpose of the Study:

  • To investigate if mtDNA-depleted cells exhibit resistance to apoptosis.
  • To explore the underlying mechanisms of this potential resistance to apoptosis.

Main Methods:

  • Comparison of parental 143B cells and mtDNA-deficient Rho˚206 cells.
  • Exposure to solar-simulated ultraviolet (UV) radiation.
  • Assessment of apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) via flow cytometry and Western blot.

Main Results:

  • UV radiation increased apoptosis and ROS production in both cell lines.
  • Rho˚206 cells showed reduced apoptosis and ROS production compared to 143B cells.
  • Lower release of cytosolic cytochrome c was observed in Rho˚206 cells.

Conclusions:

  • mtDNA-deficient Rho˚206 cells are more resistant to UV-induced apoptosis than 143B cells.
  • Decreased ROS production may explain the enhanced apoptosis resistance in mtDNA-depleted cells.

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,...
17.6K
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...
19.4K
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,...
21.2K
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
10.0K
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...
9.1K