Essential Roles of Mitochondrial Lon Protease in regulating cancer cell growth and cellular bioenerg

来源 :中国生物化学与分子生物学会2016年全国学术会议 | 被引量 : 0次 | 上传用户:wagegea
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
  Mitochondria play a primary role in cellular bioenergetics Protein homeostasis within mitochondria matrix is essential for the tumor viability.As a ATP-dependent protease located in mitochondrial matrix,Lon contributes to the degradation of abnormal proteins.Although the majority of Lon is located in mitochondrial matrix,it is also found in mitochondrial nucleoids.Lon is a stress protein and can be induced by lots of stresses such as hypoxia.The Lon up-regulation may be critical for cancer cell survival by preventing abnormal mitochondrial proteins accumulation and aggregation in response to oxidative,hypoxic,and ER stress.Our recent studies demonstrated that Lon expression was increased in cervical cancer tissues and Lon may serve as a potential therapeutic target in cervical cancer.we knocked down Lon and found drastically reduction of cancer cell proliferation and cell growth.The mtDNA encoded subunit Ⅱ of COX and the nuclear-encoded Subunit Ⅳ and Ⅴ of COX were rapidly reduced under ER stress.During hypoxia,HIF-1 activates the LON gene transcription to up-regulate Lon expression.Increased Lon degrades COX4-1 to facilitate the switch from COX4-1 to more efficient COX4-2 to challenge the low oxygen by enhancing mitochondrial respiration.Thus,Lon mediated protein degradation can relieve the heavy load of abnormal mitochondrial proteins accumulation.Moreover,down-regulation of Lon decreased mitochondrial ROS production and blocks JNK activation.we proposed that the down-regulation of Lon leads to the impairment of mitochondrial respiratory chain complexes and inhibits the mitochondrial ROS production to inhibit cancer cell proliferation.Surprisingly,Lonp1deletion causes embryonic lethality which indicated that Lon may play crucial role in embryonic development.Together,we suggest that Lon could serve as a potential diagnostic biomarker and therapeutic target for cancer treatment.
其他文献
兴安落叶松(Larix gmelinii)隶属于松科落叶松属,是中国东北、华北、西南及内蒙古地区主要的落叶乔木,其木材挺直、纹理清晰、材质致密,具有较强的机械性能,适用于做室内装饰板、家具和人造板,具有很高的经济价值,对其生长发育及木材形成调控的研究具有重要意义。
海藻糖是一种非还原性双糖,胁迫条件下可作为应激保护剂,对蛋白质和生物膜起到保护作用,海藻糖含量的升高能够增强植物对各种非生物胁迫的耐受性,具有保存生物活力的特殊功能。海藻糖-6-磷酸合酶(Tps)与海藻糖-6-磷酸磷酸酯酶(Tpp)是海藻糖代谢途径中的关键酶,Tps 和Tpp 基因的表达直接影响海藻糖的合成。
构树(Broussonetia Papyrifera(L.)Vent)为桑科(Moraceae)构树属的多年生落叶乔木;具有生长快、适应性强、分布广、易繁殖、抗污染能力强、耐烟尘污染等特点,被广泛应用于造纸、饲料、医药等行业,并在扶贫产业、环境保护生态修复上发挥重要作用.在高等植物中,多糖代谢在调控纤维素、半纤维素、果胶和胼胝质等细胞壁物质的形成、营养器官的生长及生殖器官的发育过程发挥重要作用.
王枣子为香茶菜属植物,具清热解毒、抗菌消炎等功效。目前国内外对香茶菜的研究主要集中在化学成分的提取,鉴定以及药理作用方面,对其外植体的消毒方法和打破休眠的基础性研究很少。因此本文选取成熟的王枣子种子,于11月份至次年2 月份对其外植体的消毒和种子打破休眠的方法进行研究。研究发现70%乙醇消毒1min、升汞消毒10min 的王枣子种子污染率低且萌发率高;70%乙醇消毒30 s、升汞消毒8 min 的
The desiccation tolerant desert moss Syntrichia caninervis is a potential source for genetic element that could be utilized for crop improvement for drought tolerance.An ABSCISIC ACID INSENSITIVE3(ABI
The endosomal sorting complex required for transport(ESCRT)machinery is an ancient system that mainly controls multivesicular body(MVB)biogenesis and MVBmediated membrane protein sorting.Although the
Aneuploidy,defined as unequal numbers of different chromosomes,is a large-effect genetic variant and may produce diverse cellular and organismal phenotypes.Polyploids are more permissive to chromosoma
Ethylene production has been achieved in cyanobacteria by introducing an exogenous ethylene forming enzyme(EFE)that using the TCA intermediate 2-oxoglutarate(2-OG)as one of its substrates.NtcA is a gl
Objective: This study is designed to investigate whether the Müller glial cells in diabetic retinopathy participates in the formation of retinal fibrosis and define the signaling pathways and key mole