Meiotic viral attenuation through an ancestral apoptotic pathway

Area of Science:

• Cell Biology
• Molecular Biology
• Virology

Background:

• Mitochondrial release of apoptogenic proteins is key to apoptosis.
• Endonuclease G (EndoG) is a mammalian mitochondrial nuclease involved in DNA fragmentation during cell death.
• The ancestral function of this mitochondrial release pathway remains unclear.

Purpose of the Study:

• To investigate the role of Endonuclease G homologs in non-mammalian organisms.
• To explore the function of mitochondrial protein release during meiosis in budding yeast.
• To determine if this process has a role beyond programmed cell death.

Main Methods:

• Studied meiotic sporulation in budding yeast.
• Analyzed the mitochondrial release of the Endonuclease G homolog, Nuc1.
• Assessed the impact of Nuc1 release on viral load and progeny survival.

Main Results:

• Budding yeast exhibits meiotically programmed mitochondrial release of Nuc1 during sporulation.
• Unlike mammalian EndoG's role in apoptosis, Nuc1 release is pro-survival in yeast.
• Nuc1 release attenuates cytosolic L-A and Killer double-stranded RNA mycoviruses.
• This pathway protects meiotic progeny from viral derepression consequences.

Conclusions:

• Mitochondrial release of Endonuclease G homologs has a conserved, yet divergent, function across species.
• The yeast Nuc1 pathway demonstrates a primordial role in viral defense, distinct from apoptosis.
• This finding suggests that mitochondrial release of proteins, and potentially apoptosis itself, may have originated from a survival-promoting mechanism.