Mitsopoulos Panagiotis, Lapohos Orsolya, Weraarpachai Woranontee, Antonicka Hana, Chang Yu-Han, Madrenas Joaquín
Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America.
PLoS One. 2017 Jun 27;12(6):e0179967. doi: 10.1371/journal.pone.0179967. eCollection 2017.
Mitochondria translate the RNAs for 13 core polypeptides of respiratory chain and ATP synthase complexes that are essential for the assembly and function of these complexes. This process occurs in close proximity to the mitochondrial inner membrane. However, the mechanisms and molecular machinery involved in mitochondrial translation are not fully understood, and defects in this process can result in severe diseases. Stomatin-like protein (SLP)-2 is a mainly mitochondrial protein that forms cardiolipin- and prohibitin-enriched microdomains in the mitochondrial inner membrane that are important for the formation of respiratory supercomplexes and their function. Given this regulatory role of SLP-2 in processes closely associated with the mitochondrial inner membrane, we hypothesized that the function of SLP-2 would have an impact on mitochondrial translation. 35S-Methionine/cysteine pulse labeling of resting or activated T cells from T cell-specific Slp-2 knockout mice showed a significant impairment in the production of several mitochondrial DNA-encoded polypeptides following T cell activation, including Cytb, COXI, COXII, COXIII, and ATP6. Measurement of mitochondrial DNA stability and mitochondrial transcription revealed that this impairment was at the post-transcriptional level. Examination of mitochondrial ribosome assembly showed that SLP-2 migrated in sucrose-density gradients similarly to the large ribosomal subunit but that its deletion at the genetic level did not affect mitochondrial ribosome assembly. Functionally, the impairment in mitochondrial translation correlated with decreased interleukin-2 production in activated T cells. Altogether, these data show that SLP-2 acts as a general regulator of mitochondrial translation.
线粒体负责翻译呼吸链和ATP合酶复合物中13种核心多肽的RNA，这些复合物对于这些复合体的组装和功能至关重要。这一过程在线粒体内膜附近发生。然而，线粒体翻译所涉及的机制和分子机制尚未完全了解，这一过程中的缺陷可能导致严重疾病。类stomatin蛋白（SLP）-2是一种主要存在于线粒体中的蛋白质，它在线粒体内膜中形成富含心磷脂和抑制素的微结构域，这些微结构域对于呼吸超复合物的形成及其功能非常重要。鉴于SLP-2在与线粒体内膜密切相关的过程中的这种调节作用，我们推测SLP-2的功能会对线粒体翻译产生影响。对来自T细胞特异性Slp-2基因敲除小鼠的静息或活化T细胞进行35S-甲硫氨酸/半胱氨酸脉冲标记，结果显示T细胞活化后，几种线粒体DNA编码的多肽的产生显著受损，包括细胞色素b、细胞色素氧化酶I、细胞色素氧化酶II、细胞色素氧化酶III和ATP6。对线粒体DNA稳定性和线粒体转录的测量表明，这种损伤发生在转录后水平。对线粒体核糖体组装的检查表明，SLP-2在蔗糖密度梯度中的迁移与大核糖体亚基相似，但在基因水平上删除它并不影响线粒体核糖体组装。在功能上，线粒体翻译的损伤与活化T细胞中白细胞介素-2产生的减少相关。总之，这些数据表明SLP-2作为线粒体翻译的一般调节因子发挥作用。
