A tRNA epitranscriptomic checkpoint coordinates sperm mitochondrial load with embryonic allophagic clearance.

Area of Science:

• Epigenetics
• Mitochondrial Biology
• Developmental Biology

Background:

• Strict maternal inheritance of mitochondrial DNA relies on paternal mitochondrial elimination.
• The role of epigenetic regulation in paternal mitochondrial elimination is not well understood.

Purpose of the Study:

• To investigate the role of epigenetic factors in paternal mitochondrial elimination (PME) in C. elegans.
• To identify mechanisms regulating intergenerational mitochondrial quality control.

Main Methods:

• Utilized C. elegans as a model organism.
• Investigated the function of the demethylase ALKB-1.
• Analyzed tRNA methylation patterns.
• Assessed mitochondrial proteostasis and ROS production.
• Examined stress signaling pathways (SKN-1-ATFS-1).
• Evaluated autophagic flux and PME efficiency.

Main Results:

• ALKB-1 is essential for PME in C. elegans, acting via tRNA m1A demethylation.
• ALKB-1 deficiency causes tRNA hypermethylation, disrupting mitochondrial proteostasis and increasing ROS.
• This activates stress signaling, reduces paternal mitochondria during spermatogenesis, and increases embryonic burden.
• ALKB-1 is also required in the embryo for autophagic clearance, with its loss impairing flux and delaying PME.

Conclusions:

• ALKB-1-dependent tRNA demethylation acts as a dual-germline checkpoint for mitochondrial quality control.
• This process ensures the elimination of paternal mitochondria and maintains mitochondrial health across generations.