加拿大多伦多大学Thomas R. Hurd团队近期取得重要工作进展，他们研究发现雌性生殖系统中线粒体DNA质量控制需要独特的线粒体程序性自噬来调节。相关研究成果2022年11月1日在线发表于《细胞—代谢》杂志上。

通过大规模筛选，研究人员发现了一种独特的生殖系线粒体自噬程序（PGM），PGM对mtDNA的质量控制至关重要。研究人员发现，当生殖细胞进入减数分裂时，通过抑制雷帕霉素复合体1（TORC1）的靶点，PGM被发育过程所触发。研究人员确定了RNA结合蛋白Ataxin-2（Atx2）在协调PGM与减数分裂的时间方面的作用。研究人员表明，PGM需要自噬受体BNIP3、线粒体裂变和翻译因子以及Atg1复合体的成员，而不需要自噬因子PINK1和Parkin。此外，研究人员报告了对生殖系mtDNA质量控制至关重要的几个因素，并表明对这些因素之一的药理学操作可以促进mtDNA的质量控制。

据介绍，线粒体有自己的DNA（mtDNA），容易积累致病的突变。为了防止有害基因突变被遗传，雌性生殖系进化出了一种保守的质量控制机制，但人们对这种机制还不太了解。

附：英文原文

Title: Mitochondrial DNA quality control in the female germline requires a unique programmed mitophagy

Author: Jonathan M. Palozzi, Swathi P. Jeedigunta, Anastasia V. Minenkova, Vernon L. Monteiro, Zoe S. Thompson, Toby Lieber, Thomas R. Hurd

Issue&Volume: 2022/11/01

Abstract: Mitochondria have their own DNA (mtDNA), which is susceptible to the accumulationof disease-causing mutations. To prevent deleterious mutations from being inherited,the female germline has evolved a conserved quality control mechanism that remainspoorly understood. Here, through a large-scale screen, we uncover a unique programmedgermline mitophagy (PGM) that is essential for mtDNA quality control. We find thatPGM is developmentally triggered as germ cells enter meiosis by inhibition of thetarget of rapamycin complex 1 (TORC1). We identify a role for the RNA-binding proteinAtaxin-2 (Atx2) in coordinating the timing of PGM with meiosis. We show that PGM requiresthe mitophagy receptor BNIP3, mitochondrial fission and translation factors, and membersof the Atg1 complex, but not the mitophagy factors PINK1 and Parkin. Additionally,we report several factors that are critical for germline mtDNA quality control andshow that pharmacological manipulation of one of these factors promotes mtDNA qualitycontrol.

DOI: 10.1016/j.cmet.2022.10.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00456-9