Mitochondrial Ribosome Dysfunction in Human Alveolar Type II Cells in Emphysema.
Mitochondrial Ribosome Dysfunction in Human Alveolar Type II Cells in Emphysema.
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DOI：
10.3390/biomedicines10071497
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发表时间：
2022-06-24
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肺气肿的特征是空气空间扩大和肺泡破坏。肺泡II型（ATII）细胞在线粒体中非常丰富。OXPHOS复合物由线粒体和核基因组编码的蛋白质组成。线粒体12S和16S rrna分别用于组装线粒体小亚基和大亚基。我们的目的是确定在肺气肿ATII细胞的线粒体功能障碍的机制。从对照非吸烟者、吸烟者和肺气肿患者中分离出ATII细胞。分析线粒体转录和翻译。我们还测定了miRNA的表达。肺气肿ATII细胞中ND1和UQCRC2表达水平降低。细胞核NDUFS1和SDHB水平升高，线粒体ND1转录蛋白表达降低。这些结果表明，在这种疾病的核和线粒体的化学计量损伤。我们还在肺气肿患者的ATII细胞中检测到低水平的线粒体结构蛋白MRPL48。16S rRNA表达降低，12S rRNA表达升高。此外，我们分析了miR4485-3p在该疾病中的水平。我们的研究结果表明miR-4485-3p和16S rRNA之间存在负反馈回路。所得结果提供了肺气肿ATII细胞线粒体功能障碍的分子机制。
Pulmonary emphysema is characterized by airspace enlargement and the destruction of alveoli. Alveolar type II (ATII) cells are very abundant in mitochondria. OXPHOS complexes are composed of proteins encoded by the mitochondrial and nuclear genomes. Mitochondrial 12S and 16S rRNAs are required to assemble the small and large subunits of the mitoribosome, respectively. We aimed to determine the mechanism of mitoribosome dysfunction in ATII cells in emphysema. ATII cells were isolated from control nonsmokers and smokers, and emphysema patients. Mitochondrial transcription and translation were analyzed. We also determined the miRNA expression. Decreases in ND1 and UQCRC2 expression levels were found in ATII cells in emphysema. Moreover, nuclear NDUFS1 and SDHB levels increased, and mitochondrial transcribed ND1 protein expression decreased. These results suggest an impairment of the nuclear and mitochondrial stoichiometry in this disease. We also detected low levels of the mitoribosome structural protein MRPL48 in ATII cells in emphysema. Decreased 16S rRNA expression and increased 12S rRNA levels were observed. Moreover, we analyzed miR4485-3p levels in this disease. Our results suggest a negative feedback loop between miR-4485-3p and 16S rRNA. The obtained results provide molecular mechanisms of mitoribosome dysfunction in ATII cells in emphysema.
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影响因子：
82.9
作者：
Cloonan SM;Glass K;Laucho-Contreras ME;Bhashyam AR;Cervo M;Pabón MA;Konrad C;Polverino F;Siempos II;Perez E;Mizumura K;Ghosh MC;Parameswaran H;Williams NC;Rooney KT;Chen ZH;Goldklang MP;Yuan GC;Moore SC;Demeo DL;Rouault TA;D'Armiento JM;Schon EA;Manfredi G;Quackenbush J;Mahmood A;Silverman EK;Owen CA;Choi AM
通讯作者：
Choi AM
DOI：
10.1074/jbc.ra118.005433
发表时间：
2018-12-21
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang J;Liu P;Wang G
通讯作者：
Wang G
DOI：
10.3390/antiox7010013
发表时间：
2018-01-16
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Ježek J;Cooper KF;Strich R
通讯作者：
Strich R
影响因子：
29
作者：
Arroyo JD;Jourdain AA;Calvo SE;Ballarano CA;Doench JG;Root DE;Mootha VK
通讯作者：
Mootha VK
影响因子：
3.5
作者：
Davies, Stefan M. K.;Rackham, Oliver;Filipovska, Aleksandra
通讯作者：
Filipovska, Aleksandra