目前,，研究人員深入探索了線粒體中的基因功能異常,。線粒體是機(jī)體生成能量的場(chǎng)所，其功能對(duì)生命來說是必須的,，所以線粒體的功能缺失可能會(huì)影響人類和動(dòng)物中一系列的器官系統(tǒng),。
一些常見的線粒體異常疾病包括利氏病，MELAS綜合癥和復(fù)合物1缺陷等,，這些疾病通常是嚴(yán)重的，而且會(huì)不斷發(fā)展導(dǎo)致大腦,，肌肉和機(jī)體許多其他的部位功能失調(diào),。
線粒體疾病相對(duì)比較罕見,，但是也存在不少的病例。大部分的疾病都?xì)w因于線粒體內(nèi)部,，線粒體故障同樣會(huì)導(dǎo)致一些復(fù)雜的紊亂,，比如帕金森氏癥，老年癡呆癥,，癲癇和糖尿病等,。其中許多生物學(xué)原因還不是很清楚，比如線粒體如何正確地執(zhí)行功能,。一項(xiàng)發(fā)布在8月12日PLoS ONE上的新研究報(bào)告,，解釋了最新的線粒體生物學(xué)研究進(jìn)展。
使用基因工程技術(shù),，研究人員阻斷了個(gè)別基因的活性,，這些基因能直接參與線粒體中能量的產(chǎn)生。這項(xiàng)研究的負(fù)責(zé)人Marni J. Falk博士介紹說,，他們希望通過阻止這種特殊的系統(tǒng)元件的功能,，觀察結(jié)果的變化，最終的目的是,，希望能為靶向治療提供生物學(xué)依據(jù),。但是首先需要理解潛在的疾病機(jī)制。
Falk的團(tuán)隊(duì)利用一種簡(jiǎn)單的模式生物-秀麗隱桿線蟲進(jìn)行該項(xiàng)研究,。研究人員解釋說,，理解秀麗隱桿線蟲中線粒體功能的詳細(xì)信息能為人類細(xì)胞線粒體的功能研究提供線索。
研究人員觀察了線粒體中的一個(gè)生物學(xué)通路,，即呼吸鏈,，特別關(guān)注了這條鏈最大的組成成分，復(fù)合物I,，其包含45個(gè)亞單元,，并對(duì)其中的28個(gè)亞單元的核基因（這些基因與人類和大腸桿菌中基因很相似），作了研究,。他們使用RNA干擾技術(shù),，敲除每一個(gè)基因的功能，以確定基因缺失導(dǎo)致的相關(guān)的線粒體疾病,。
結(jié)果發(fā)現(xiàn),，其中一組基因的子集減弱了線粒體消耗氧的能力，另一組基因則影響了線蟲對(duì)貧血的應(yīng)答能力,。
由于線粒體疾病在人類中有許多不同的紊亂,，因此理解呼吸鏈中不同基因?qū)е碌漠惓⒂兄谘芯咳藛T更好的理解人類線粒體機(jī)能障礙導(dǎo)致的不同問題，同時(shí)也可為潛在的靶向治療提供依據(jù)。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS ONE 4(8): e6607. doi:10.1371/journal.pone.0006607
Subcomplex Iλ Specifically Controls Integrated Mitochondrial Functions in Caenorhabditis elegans
Marni J. Falk1*, Julie R. Rosenjack2, Erzsebet Polyak1, Wichit Suthammarak2, Zhongxue Chen3, Phil G. Morgan2,4, Margaret M. Sedensky2,4
1 Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Department of Anesthesiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America, 3 Biostatistics & Data Management Core, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America, 4 Department of Anesthesiology, Seattle Children's Regional Medical Center and University of Washington, Seattle, Washington, United States of America
Complex I dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. The extensive conservation of complex I composition between humans and Caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at both the whole animal and mitochondrial levels. We provide the first experimentally-verified compilation of complex I composition in C. elegans, demonstrating 84% conservation with human complex I. Individual subunit contribution to mitochondrial respiratory capacity, holocomplex I assembly, and animal anesthetic behavior was studied in C. elegans by RNA interference-generated knockdown of nuclear genes encoding 28 complex I structural subunits and 2 assembly factors. Not all complex I subunits directly impact respiratory capacity. Subcomplex Iλ subunits along the electron transfer pathway specifically control whole animal anesthetic sensitivity and complex II upregulation, proportionate to their relative impairment of complex I-dependent oxidative capacity. Translational analysis of complex I dysfunction facilitates mechanistic understanding of individual gene contribution to mitochondrial disease. We demonstrate that functional consequences of complex I deficiency vary with the particular subunit that is defective.
