Sperm-inherited organelle clearance in C. elegans relies on LC3-dependent autophagosome targeting to the pericentrosomal area.
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.
Sorbonne Universités, UPMC, Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR7622, Paris F-75005, France CNRS, IBPS, UMR7622, Paris F-75005, France.
Abderazak
A
Djeddi
Sorbonne Universités, UPMC, Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR7622, Paris F-75005, France CNRS, IBPS, UMR7622, Paris F-75005, France.
Sara
S
Al Rawi
Sorbonne Universités, UPMC, Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR7622, Paris F-75005, France CNRS, IBPS, UMR7622, Paris F-75005, France.
Jane Lynda
JL
Deuve
Sorbonne Universités, UPMC, Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR7622, Paris F-75005, France CNRS, IBPS, UMR7622, Paris F-75005, France.
Charlene
C
Perrois
Sorbonne Universités, UPMC, Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR7622, Paris F-75005, France CNRS, IBPS, UMR7622, Paris F-75005, France.
Yu-Yu
YY
Liu
Sorbonne Universités, UPMC, Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR7622, Paris F-75005, France CNRS, IBPS, UMR7622, Paris F-75005, France.
Marion
M
Russeau
PFMU, Imagopole, Institut Pasteur, Paris F-75015, France.
Martin
M
Sachse
Sorbonne Universités, UPMC, Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UMR7622, Paris F-75005, France CNRS, IBPS, UMR7622, Paris F-75005, France vgaly@snv.jussieu.fr.
Vincent
V
Galy
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D005111:Extrachromosomal Inheritance / Q000502:physiology; D005455:Fluorescent Antibody Technique; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism*; D034622:RNA Interference; D013094:Spermatozoa / Q000166:cytology*
D029742:Caenorhabditis elegans Proteins; C587195:LGG-1 protein, C elegans; C587196:LGG-2 protein, C elegans; D008869:Microtubule-Associated Proteins
Allophagy; Autophagy; Fertilization; LC3; LGG-2; MtDNA transmission