Allophagy: a macroautophagic process degrading spermatozoid-inherited organelles

Abstract

In most animals, during oocyte fertilization the spermatozoon provides DNA and centrioles together with some cytoplasm and organelles, but paternal mitochondria are generally eliminated in the embryo. Using the model animal C. elegans we have shown that paternal organelle degradation is dependent on the formation of autophagosomes a few minutes after fertilization. This macroautophagic process is preceded by an active ubiquitination of some spermatozoon-inherited organelles. Analysis of fertilized mouse embryos suggests that this autophagy event is evolutionarily conserved.

Figure 1. Transmission electron micrographs of a C. elegans spermatozoid (A) showing its DNA, membranous organelles (MO) and mitochondria (mt) prior to fertilization, and of the cortical area of a two-cell stage embryo (B) revealing the presence of autophagosomes around mitochondria. The white and black arrows indicate the limiting double membrane. Scale bars are 500 nm in (A and B). (C and D) Schematic view of the allophagy process. After fertilization, spermatozoon-inherited mitochondria and membranous organelles are engulfed in autophagosomes and degraded during the first zygote divisions (C). Interfering with autophagosome formation or fusion with lysosomes (not described) stabilizes spermatozoon-inherited organelles (D). (E) The entry of spermatozoid organelles in the mouse oocyte at fertilization induces ubiquitination and recruitment of autophagy markers (LC3) around the flagellum mid-piece still attached to the nuclear DNA. Scale bar is 5 μm in (E). (B) is adapted from Figure 1E, and (E) is adapted from Figures S5F and S5H of Al Rawi S, Louvet-Vallée S, Djeddi A, Sachse M, Culetto E, Hajjar C, Boyd L, Legouis R, Galy V. Science 2011; 334:1144–7.