Department of Medicine, Nephrology Division, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Developmental Biology Laboratory, Sorbonne Université, CNRS, Institut de Biologie Paris Seine, IBPS, UMR7622, Paris, France.
Dev Biol. 2019 Oct 1;454(1):15-20. doi: 10.1016/j.ydbio.2019.06.016. Epub 2019 Jun 21.
Paternal mitochondria are eliminated following fertilization by selective autophagy, but the mechanisms that restrict this process to sperm-derived organelles are not well understood. FUNDC1 (FUN14 domain containing 1) is a mammalian mitophagy receptor expressed on the mitochondrial outer membrane that contributes to mitochondrial quality control following hypoxic stress. Like FUNDC1, the C. elegans ortholog FNDC-1 is widely expressed in somatic tissues and mediates hypoxic mitophagy. Here, we report that FNDC-1 is strongly expressed in sperm but not oocytes and contributes to paternal mitochondria elimination. Paternal mitochondrial DNA is normally undetectable in wildtype larva, but can be detected in the cross-progeny of fndc-1 mutant males. Moreover, loss of fndc-1 retards the rate of paternal mitochondria degradation, but not that of membranous organelles, a nematode specific membrane compartment whose fusion is required for sperm motility. This is the first example of a ubiquitin-independent mitophagy receptor playing a role in the selective degradation of sperm mitochondria.
父系线粒体在受精后通过选择性自噬被消除，但限制这一过程仅限于精子来源的细胞器的机制尚不清楚。FUNDC1（含 FUN14 结构域的 1 号）是一种在哺乳动物线粒体膜上表达的线粒体自噬受体，在缺氧应激后有助于线粒体质量控制。与 FUNDC1 一样，C. elegans 的同源物 FNDC-1 在体组织中广泛表达，并介导缺氧诱导的线粒体自噬。在这里，我们报告 FNDC-1 在精子中强烈表达，但在卵母细胞中不表达，并有助于父系线粒体的消除。在野生型幼虫中，父系线粒体 DNA 通常无法检测到，但在 fndc-1 突变体雄性的杂交后代中可以检测到。此外，fndc-1 的缺失会减缓父系线粒体的降解速度，但不会减缓膜细胞器的降解速度，膜细胞器是一种线虫特有的膜隔室，其融合对于精子运动是必需的。这是第一个非泛素依赖的线粒体自噬受体在精子线粒体的选择性降解中发挥作用的例子。
