Sperm-inherited organelle clearance inC. elegansrelies on LC3-dependent autophagosome targeting to the pericentrosomal area

• DOI: 10.1242/dev.117879
• Publication Date: 2015-04-28T11:20:28Z
• Authors: Abderazak Djeddi; Sara Al Rawi; Jane Lynda Deuve; Charlene Perrois; Yu-Yu Liu; Marion Russeau; Martin Sachse; Vincent Galy
• Keywords: Male; Organelles; 0301 basic medicine; Extrachromosomal Inheritance; Fluorescent Antibody Technique; Biological Transport; MtDNA transmission; Spermatozoa; [SDV] Life Sciences [q-bio]; 03 medical and health sciences; Microscopy, Electron, Transmission; Fertilization; LGG-2; [SDV.BDD] Life Sciences [q-bio]/Development Biology; LC3; Autophagy; Animals; RNA Interference; Allophagy; Caenorhabditis elegans; Caenorhabditis elegans Proteins; [SDV.BDD]Life Sciences [q-bio]/Development Biology; Microtubule-Associated Proteins

Macroautophagic degradation of sperm-inherited organelles prevents paternal mitochondrial DNA transmission in C. elegans. The recruitment of autophagy markers around sperm mitochondria has also been observed in mouse and fly embryos but their role in degradation is debated. Both worm Atg8 ubiquitin-like proteins, LGG-1/GABARAP and LGG-2/LC3, are recruited around sperm organelles after fertilization. Whereas LGG-1 depletion affects autophagosome function, stabilizes the substrates and is lethal, we demonstrate that LGG-2 is dispensable for autophagosome formation but participates in their microtubule-dependent transport toward the pericentrosomal area prior to acidification. In the absence of LGG-2, autophagosomes and their substrates remain clustered at the cell cortex, away from the centrosomes and their associated lysosomes. Thus, the clearance of sperm organelles is delayed and their segregation between blastomeres prevented. This allowed us to reveal a role of the RAB-5/RAB-7 GTPases in autophagosome formation. In conclusion, the major contribution of LGG-2 in sperm-inherited organelle clearance resides in its capacity to mediate the retrograde transport of autophagosomes rather than their fusion with acidic compartments: a potential key function of LC3 in controlling the fate of sperm mitochondria in other species.