线粒体-内质网接触膜结构(MAMs,mitochondria associated ER membranes)是线粒体外膜和内质网膜之间相距约10-30nm的一种空间结构，被证实参与调控线粒体和内质网之间的物质交换而与多种人类疾病的发生发展密切相关，但在精子发生过程中的功能及作用仍未见报道。我们前期研究发现MAM大量存在于小鼠和人睾丸组织中，并纯化了MAM进行LC/MS分析，鉴定得到睾丸特异MAM蛋白815个，但这些MAM蛋白的具体生理功能及调控机制尚未解析。本项目拟从两方面开展工作：一是利用已有的LC/MS数据对小鼠和人睾丸MAM做进一步鉴定，挖掘新的关键分子及调控网络；二是通过已成功构建的睾丸MAM蛋白MFN1和MFN2的生殖细胞条件性敲除小鼠模型，检测MAM的结构和功能变化，阐明其调控精子发生的分子机理。通过本项目的研究，可望解析MAM蛋白在精子发生和男性不育症中的生理功能及机制。

Mitochondria–ER contacts are defined as regions where two membranes are closely apposed but the membranes do not fuse (10-30nm), known as mitochondria-associated ER membranes (MAMs). It has been reported that MAMs regulates several important cellular functions by regulating the substance exchanges between mitochondria and ER, and its abnormality usually associates to several human diseases, however, its function during spermatogenesis is still elusive. Previously, we observed the existence of MAMs in male germ cells, purified MAM structure and identified 815 testis-specific MAM proteins, but the molecular function of testis MAMs is unexplored during spermatogenesis. To address the biological function and molecular mechanism of MAMs during spermatogenesis, in this project, we will accordingly study: (1) Confirmation of novel identified MAM proteins in mouse and human testes by LC/MS technique, and exploring critical molecule and regulation network of MAMs in regulating spermatogenesis; (2) Investigate the structural and functional changes of MAM by employing MAM protein-coding genes Mfn1 and Mfn2 using conditional knockout mouse models. The findings of this proposal will be helpful to reveal the novel underlying regulatory mechanisms and biological functions of the interaction between mitochondria and ER in spermatogenesis and male infertility.