High Sucrose Diet-Induced Subunit I Tyrosine 304 Phosphorylation of Cytochrome c Oxidase Leads to Liver Mitochondrial Respiratory Dysfunction in the Cohen Diabetic Rat Model.
High Sucrose Diet-Induced Subunit I Tyrosine 304 Phosphorylation of Cytochrome c Oxidase Leads to Liver Mitochondrial Respiratory Dysfunction in the Cohen Diabetic Rat Model.
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DOI：
10.3390/antiox13010019
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发表时间：
2023-12-21
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影响因子：
--
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线粒体氧化磷酸化过程在哺乳动物组织中产生大部分细胞能量和自由基。这两个因素在众多人类疾病中都起着关键作用，这些疾病可能受到调节氧化磷酸化复合物功能和活性的可逆磷酸化事件的影响。在这项研究中，我们分析了科恩糖尿病敏感（CDs）和科恩糖尿病抵抗（CDr）大鼠的肝脏线粒体，使用蓝色天然凝胶电泳（BN - PAGE）结合线粒体活性测量以及一种与炎症有关的位点特异性酪氨酸磷酸化（炎症是已知的糖尿病病理驱动因素）。我们发现二聚体细胞色素c氧化酶（CcO，复合物IV）催化亚基I的酪氨酸304上存在一种特异性抑制性磷酸化。在CDr和CDs大鼠中，高蔗糖饮食驱动下，发生在靠近催化氧结合位点的Y304磷酸化，与高血糖条件下大鼠肝脏组织中CcO活性降低和呼吸功能障碍相关。我们提出，这种磷酸化（特别是在二聚体CcO中观察到且由高蔗糖饮食介导的炎症信号诱导）引发复合物IV二聚体的酶活性下降以及肝脏组织中超级复合物的组装，这是（前）糖尿病表型的一种分子机制。
The mitochondrial oxidative phosphorylation process generates most of the cellular energy and free radicals in mammalian tissues. Both factors play a critical role in numerous human diseases that could be affected by reversible phosphorylation events that regulate the function and activity of the oxidative phosphorylation complexes. In this study, we analyzed liver mitochondria of Cohen diabetes-sensitive (CDs) and Cohen diabetes-resistant (CDr) rats, using blue native gel electrophoresis (BN-PAGE) in combination with mitochondrial activity measurements and a site-specific tyrosine phosphorylation implicated in inflammation, a known driver of diabetes pathology. We uncovered the presence of a specific inhibitory phosphorylation on tyrosine 304 of catalytic subunit I of dimeric cytochrome c oxidase (CcO, complex IV). Driven by a high sucrose diet in both CDr and CDs rats, Y304 phosphorylation, which occurs close to the catalytic oxygen binding site, correlates with a decrease in CcO activity and respiratory dysfunction in rat liver tissue under hyperglycemic conditions. We propose that this phosphorylation, specifically seen in dimeric CcO and induced by high sucrose diet-mediated inflammatory signaling, triggers enzymatic activity decline of complex IV dimers and the assembly of supercomplexes in liver tissue as a molecular mechanism underlying a (pre-)diabetic phenotype.
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影响因子：
4.6
作者：
Araujo, Mizael C.;Soczek, Suzany H. S.;Pontes, Jaqueline P.;Pinto, Bruno A. S.;Franca, Lucas M.;Soley, Bruna da Silva;Santos, Gabriela S.;Saminez, Warlison F. de Silva;Fernandes, Fernanda K. M.;Lima, Joao L. do Carmo;Maria-Ferreira, Daniele;Rodrigues, Joao F. S.;Quintao, Nara L. M.;Monteiro-Neto, Valerio;Paes, Antonio M. A.;Fernandes, Elizabeth S.
通讯作者：
Fernandes, Elizabeth S.
影响因子：
4.8
作者：
Samavati, Lobelia;Lee, Icksoo;Huttemann, Maik
通讯作者：
Huttemann, Maik
影响因子：
6
作者：
Aharon-Hananel G;Romero-Afrima L;Saada A;Mantzur C;Raz I;Weksler-Zangen S
通讯作者：
Weksler-Zangen S
影响因子：
6
作者：
通讯作者：
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DOI：
10.1016/j.biocel.2020.105704
发表时间：
2020-04-01
影响因子：
4
作者：
Kalpage, Hasini A.;Wan, Junmei;Huttemann, Maik
通讯作者：
Huttemann, Maik