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The Intrinsic Apoptotic Pathway01:31

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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...
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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...
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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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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...
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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...
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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...
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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
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Apoptotic Factors Are Evolutionarily Conserved Since Mitochondrial Domestication.

Vandana Kaushal1, Joanna Klim1, Adrianna Skoneczna1

  • 1Institute of Biochemistry and Biophysics PAS, Pawinskiego 5a, 02-106 Warszawa, Poland.

Genome Biology and Evolution
|August 24, 2023
PubMed
Summary

The study found that proteins from bacteria and diverse eukaryotes can trigger programmed cell death (apoptosis) in yeast, supporting the endosymbiotic origin of apoptosis and its ancient evolutionary roots.

Keywords:
apoptosisapoptotic factorsmitochondrial domesticationortholog complementationyeast

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Area of Science:

  • Cell Biology
  • Evolutionary Biology
  • Genetics

Background:

  • Apoptotic programmed cell death mechanisms are conserved across eukaryotes.
  • These mechanisms involve mitochondrial permeability transition, activating proteases, DNases, and flavoproteins.
  • The endosymbiotic theory proposes these evolved during mitochondrial domestication from eubacterial toxins.

Purpose of the Study:

  • To investigate if eubacterial and distantly related eukaryotic orthologs can substitute for yeast apoptotic factors.
  • To test the hypothesis of the endosymbiotic origin of apoptosis.

Main Methods:

  • Functional analysis of yeast Saccharomyces cerevisiae apoptotic proteases (metacaspases Mca1, Nma111), DNase (Nuc1), and flavoprotein (Ndi1).
  • Substitution assays using orthologs from plants, protists, and eubacteria.
  • Induction of apoptosis via chemical stresses in yeast models.

Main Results:

  • Orthologs from diverse eukaryotes and eubacteria successfully initiated apoptosis in yeast.
  • Functional conservation of apoptotic factors across vast evolutionary distances was demonstrated.
  • Evidence supports the ancient maintenance of apoptotic mechanisms since mitochondrial domestication (~1,800 Mya).

Conclusions:

  • Apoptotic mechanisms are evolutionarily conserved since mitochondrial domestication.
  • The findings support the hypothesis that some apoptotic factors originated as eubacterial toxins.