Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2

Sona Hubackova1, Eliska Davidova2, Katerina Rohlenova2,3

  • 1Laboratory of Molecular Therapy, Institute of Biotechnology, Czech Academy of Sciences, Prague, 252 50, Czech Republic. sona.hubackova@ibt.cas.cz.

Insights

Mitochondria-targeted tamoxifen (MitoTam) eliminates senescent cells, unlike conventional drugs. This novel anticancer agent offers a potential strategy for treating age-related diseases and senescence-associated pathologies by targeting adenine nucleotide translocase-2 (ANT2) expression.

Area of Science:

  • Cellular biology
  • Aging research
  • Oncology

Background:

  • Cellular senescence is a state of irreversible cell cycle arrest.
  • Accumulation of senescent cells contributes to tissue damage, inflammation, and age-related diseases.
  • Current anticancer therapies may induce senescence, complicating treatment outcomes.

Purpose of the Study:

  • To investigate the effects of mitochondria-targeted tamoxifen (MitoTam) on senescent cells.
  • To explore the potential of MitoTam as a therapeutic agent for senescence-associated conditions.
  • To elucidate the mechanism underlying senescent cell susceptibility to MitoTam.

Main Methods:

  • In vitro and in vivo experiments using cancer cells and aged mice.
  • Treatment with MitoTam and conventional anticancer agents.
  • Analysis of senescence markers and adenine nucleotide translocase-2 (ANT2) expression.
  • Genetic manipulation of ANT2 levels in senescent and non-senescent cells.

Main Results:

  • MitoTam eliminates cancer cells without inducing senescence.
  • MitoTam selectively eliminates both malignant and non-cancerous senescent cells.
  • A significant decrease in senescence markers was observed in aged mice treated with MitoTam.
  • Senescent cells' susceptibility to MitoTam is linked to low ANT2 expression.

Conclusions:

  • MitoTam presents a novel therapeutic strategy for eliminating senescent cells.
  • Targeting mitochondrial pathways offers a new approach for treating age-related diseases and senescence-associated pathologies.
  • ANT2 expression levels are critical in determining senescent cell sensitivity to MitoTam.

Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.4K
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...
9.3K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
pH Regulation in Cells01:28

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
7.8K
Export of Mitochondrial and Chloroplast Genes02:19

Export of Mitochondrial and Chloroplast Genes

A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
4.2K
Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes02:16

Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes

The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
16.8K