Petrović V, Korać A, Buzadzić B, Vasilijević A, Janković A, Mićunović K, Korać B
Department of Physiology, Institute for Biological Research, Sinisa Stanković, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
J Microsc. 2008 Dec;232(3):542-8. doi: 10.1111/j.1365-2818.2008.02132.x.
As a complex, cell-specific process that includes both division and clear functional differentiation of mitochondria, mitochondriogenesis is regulated by numerous endocrine and autocrine factors. In the present ultrastructural study, in vivo effects of L-arginine-nitric oxide (NO)-producing pathway on mitochondriogenesis in interscapular brown adipose tissue (IBAT) were examined. For that purpose, adult Mill Hill hybrid hooded rats were receiving L-arginine, a substrate of NO synthases (NOSs), or N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOSs, as drinking liquids for 45 days. All experimental groups were divided into two sub-groups - acclimated to room temperature and cold. IBAT mitochondria were analyzed by transmission electron microscopy and stereology. L-Arginine treatment acted increasing the number of mitochondrial profiles per cell profile, as well as volume fraction of mitochondria per cell volume in animals maintained at room temperature. Cold-induced enhancement of number of mitochondrial profiles per cell profile was additionally increased in L-arginine-treated rats. Ultrastructural examinations of L-arginine-treated cold-acclimated animals clearly demonstrated thermogenically active mitochondria (larger size, lamellar, more numerous and well-ordered cristae in their profiles), which however were inactive in L-arginine-receiving animals kept at room temperature (small mitochondria, tubular cristae). By contrast, L-NAME treatment of rats acclimated to room temperature induced mitochondrial alterations characterized by irregular shape, short disorganized cristae and megamitochondria formation. These results showed that NO is a necessary factor for mitochondrial biogenesis and that it acts intensifying this process, but NO alone is not a sufficient stimulus for in vivo induction of mitochondriogenesis in brown adipocytes.
线粒体生成是一个复杂的、细胞特异性的过程，包括线粒体的分裂和明确的功能分化，受到多种内分泌和自分泌因子的调节。在本超微结构研究中，检测了L-精氨酸-一氧化氮（NO）产生途径对肩胛间棕色脂肪组织（IBAT）线粒体生成的体内影响。为此，成年米尔希尔杂交带帽大鼠将L-精氨酸（NO合酶（NOSs）的底物）或NOSs抑制剂N（ω）-硝基-L-精氨酸甲酯（L-NAME）作为饮用水饮用45天。所有实验组分为两个亚组——适应室温组和寒冷组。通过透射电子显微镜和体视学分析IBAT线粒体。L-精氨酸处理使室温饲养动物的每个细胞轮廓中线粒体轮廓的数量增加，以及每个细胞体积中线粒体的体积分数增加。在L-精氨酸处理的大鼠中，寒冷诱导的每个细胞轮廓中线粒体轮廓数量的增加进一步增强。对L-精氨酸处理的冷适应动物的超微结构检查清楚地显示出产热活跃的线粒体（尺寸更大，呈板层状，其轮廓中的嵴更丰富且排列有序），然而在室温饲养的接受L-精氨酸的动物中这些线粒体是不活跃的（小线粒体，管状嵴）。相比之下，对适应室温的大鼠进行L-NAME处理会诱导线粒体改变，其特征为形状不规则、嵴短且紊乱以及形成巨型线粒体。这些结果表明，NO是线粒体生物发生的必要因素，并且它在强化这一过程中起作用，但单独的NO并不是体内诱导棕色脂肪细胞线粒体生成的充分刺激因素。
