An aggregated mitochondrial distribution in preimplantation embryos disrupts nuclear morphology, function, and developmental potential

• 成果类型: Article
• 署名作者: Lee, In-Won; Tazehkand, Abbas Pirpour; Sha, Zi-Yi; Adhikari, Deepak; Carroll, John
• 署名单位: Monash University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10003
• DOI: 10.1073/pnas.2317316121
• 发表日期: 2024-07-02
• 关键词: mouse oocytes; axonal-transport; primordial follicles; cell-division; inheritance; milton; TRAFFICKING; expression; actin; dna

摘要

A dispersed cytoplasmic distribution of mitochondria is a hallmark of normal cellular organization. Here, we have utilized the expression of exogenous Trak2 in mouse oocytes and embryos to disrupt the dispersed distribution of mitochondria by driving them into a large cytoplasmic aggregate. Our findings reveal that aggregated mitochondria have minimal impact on asymmetric meiotic cell divisions of the oocyte. In contrast, aggregated mitochondria during the first mitotic division result in daughter cells with unequal sizes and increased micronuclei. Further, in two - cell embryos, microtubule - mediated centering properties of the mitochondrial aggregate prevent nuclear centration, distort nuclear shape, and inhibit DNA synthesis and the onset of embryonic transcription. These findings demonstrate the motor protein - mediated distribution of mitochondria throughout the cytoplasm is highly regulated and is an essential feature of cytoplasmic organization to ensure optimal cell function.