活性氧的去毒作用
中文名称
通路描述
超氧化物（O2.-）、过氧化物（ROOR）、单线态氧、过氧亚硝酸盐（ONOO-）和羟基自由基（OH。）等活性氧物种由细胞过程如呼吸（Murphy 2009, Brand 2010）和氧化还原酶产生，它们既是信号分子又是有害的，因为它们的反应性高（Imlay 2008, Buettner 2011, Kavdia 2011, Birben et al. 2012, Ray et al. 2012）。有氧细胞通过将其转化为反应性较低的产品来解毒活性氧。超氧化物歧化酶将超氧化物转化为过氧化氢和氧气（Fukai and Ushio-Fukai 2011）。过氧化氢酶和过氧化物酶则将过氧化氢转化为水。人类含有三种超氧化物歧化酶：SOD1 位于细胞质和线粒体间质，SOD2 位于线粒体基质，SOD3 位于细胞外区域。超氧化物是一种负离子，难以穿过膜，倾向于留在产生它的隔室中。过氧化氢是超氧化物歧化酶的产物之一，能够穿过膜并通过水通道蛋白扩散。在大多数细胞中，过氧化氢的主要来源是线粒体，一旦进入细胞质，它作为信号分子调节氧化还原敏感的蛋白质，如转录因子、激酶、磷酸酶、离子通道等（Veal and Day 2011, Ray et al. 2012）。过氧化氢由过氧化氢酶分解为水，由过氧化物酶分解为水和氧化型谷胱甘肽，由谷胱甘肽过氧化物酶分解为水和氧化型谷胱甘肽（Presnell et al. 2013）。
英文描述
Mitochondrial mRNA modification Mitochondrial mRNAs contain polyadenylation, pseudouridylation, and N1-adenosine methylation, posttranscriptional modifications that are catalyzed by proteins encoded in the nucleus (reviewed in Chrzanowska-Lightowlers and Lightowlers 2024).
Polyadenylation at the 3' ends of mitochondrial mRNAs is produced by MTPAP (also called PAPD1), a dimeric polyadenylate polymerase located in both the cytosol and the mitochondrial matrix (Nagaike et al. 2005, Slomovic and Schuster 2008, Bai et al. 2011, Wilson et al. 2014, reviewed in Chang and Tong 2012). Like the polyadenylate tails of cytoplasmic mRNAs, the mitochondrial polyadenylate tails appear to stabilize the mRNAs (Nagaike et al. 2005), however, mitochondrial polyadenylate tails (~40-50 adenylate residues) are shorter than those observed in the cytosol (~250 adenylate residues) (reviewed in BoreikaitÄ and Passmore 2023). MTPAP may also catalyze polyuridylation.
Pseudouridylation in mitochondria is catalyzed by a large protein complex, the mitochondrial pseudouridylation module, that contains the pseudouridine synthases RPUSD3, RPUSD4, and TRUB2 (Arroyo et al. 2016, Antonicka et al. 2017). RPUSD4 pseudouridylates rRNA and tRNA while either RPUSD3 or TRUB2 are capable of pseudouridylating uridine-390 of MT-CO1 mRNA and uridine-697 of MT-CO3 mRNA (Carlile et al. 2019, Antonicka et al. 2017). Depletion of either RPUSD3 or TRUB2 caused a reduction in mitochondrial translation (Antonicka et al. 2017).
In mitochondria, methylation of the N1 position of adenosine residues in mRNAs is catalyzed by the methyltransferase TRMT61B, which methylates adenosine residues in the MT-ND1, MT-CO1, MT-CO2, MT-CO3, MT-ND4L, and MT-CYB mRNAs (Li et al. 2017). N1-methyladenosine in mitochondrial mRNAs causes ribosome stalling and reduced translation (Li et al. 2017).
Polyadenylation at the 3' ends of mitochondrial mRNAs is produced by MTPAP (also called PAPD1), a dimeric polyadenylate polymerase located in both the cytosol and the mitochondrial matrix (Nagaike et al. 2005, Slomovic and Schuster 2008, Bai et al. 2011, Wilson et al. 2014, reviewed in Chang and Tong 2012). Like the polyadenylate tails of cytoplasmic mRNAs, the mitochondrial polyadenylate tails appear to stabilize the mRNAs (Nagaike et al. 2005), however, mitochondrial polyadenylate tails (~40-50 adenylate residues) are shorter than those observed in the cytosol (~250 adenylate residues) (reviewed in BoreikaitÄ and Passmore 2023). MTPAP may also catalyze polyuridylation.
Pseudouridylation in mitochondria is catalyzed by a large protein complex, the mitochondrial pseudouridylation module, that contains the pseudouridine synthases RPUSD3, RPUSD4, and TRUB2 (Arroyo et al. 2016, Antonicka et al. 2017). RPUSD4 pseudouridylates rRNA and tRNA while either RPUSD3 or TRUB2 are capable of pseudouridylating uridine-390 of MT-CO1 mRNA and uridine-697 of MT-CO3 mRNA (Carlile et al. 2019, Antonicka et al. 2017). Depletion of either RPUSD3 or TRUB2 caused a reduction in mitochondrial translation (Antonicka et al. 2017).
In mitochondria, methylation of the N1 position of adenosine residues in mRNAs is catalyzed by the methyltransferase TRMT61B, which methylates adenosine residues in the MT-ND1, MT-CO1, MT-CO2, MT-CO3, MT-ND4L, and MT-CYB mRNAs (Li et al. 2017). N1-methyladenosine in mitochondrial mRNAs causes ribosome stalling and reduced translation (Li et al. 2017).
所含基因
11 个基因