更新于：2024-11-01

交替氧化酶

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与交替氧化酶相关的药物

LN002

靶点

交替氧化酶

作用机制

交替氧化酶抑制剂

在研机构

华南农业大学

原研机构

华南农业大学

在研适应症

隐孢子虫病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

T-107175

靶点

交替氧化酶

作用机制

交替氧化酶抑制剂

在研机构-

原研机构

University of Nagasaki

在研适应症-

非在研适应症

布氏锥虫感染

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与交替氧化酶相关的临床结果

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100 项与交替氧化酶相关的转化医学

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0 项与交替氧化酶相关的专利（医药）

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411

项与交替氧化酶相关的文献（医药）

2024-09-01·Gene Therapy

Correction: Alternative oxidase encoded by sequence-optimized and chemically-modified RNA transfected into mammalian cells is catalytically active

作者: Giordano, Luca ; Aneja, Manish K ; Rudolph, Carsten ; Plank, Christian ; Sommer, Natascha ; Seraji, Alireza ; Jacobs, Howard T ; Alebrahimdehkordi, Nasim ; Szibor, Marten ; Weissmann, Norbert

2024-06-18·Proceedings of the National Academy of Sciences

Alternative oxidase blunts pseudohypoxia and photoreceptor degeneration due to RPE mitochondrial dysfunction

Article

作者: Vollrath, Douglas ; Chen, Ming ; Dalal, Roopa ; Wang, Yekai ; Du, Jianhai

Loss of mitochondrial electron transport complex (ETC) function in the retinal pigment epithelium (RPE) in vivo results in RPE dedifferentiation and progressive photoreceptor degeneration, and has been implicated in the pathogenesis of age-related macular degeneration. Xenogenic expression of alternative oxidases in mammalian cells and tissues mitigates phenotypes arising from some mitochondrial electron transport defects, but can exacerbate others. We expressed an alternative oxidase from Ciona intestinalis (AOX) in ETC-deficient murine RPE in vivo to assess the retinal consequences of stimulating coenzyme Q oxidation and respiration without ATP generation. RPE-restricted expression of AOX in this context is surprisingly beneficial. This focused intervention mitigates RPE mTORC1 activation, dedifferentiation, hypertrophy, stress marker expression, pseudohypoxia, and aerobic glycolysis. These RPE cell autonomous changes are accompanied by increased glucose delivery to photoreceptors with attendant improvements in photoreceptor structure and function. RPE-restricted AOX expression normalizes accumulated levels of succinate and 2-hydroxyglutarate in ETC-deficient RPE, and counteracts deficiencies in numerous neural retinal metabolites. These features can be attributed to the activation of mitochondrial inner membrane flavoproteins such as succinate dehydrogenase and proline dehydrogenase, and alleviation of inhibition of 2-oxyglutarate-dependent dioxygenases such as prolyl hydroxylases and epigenetic modifiers. Our work underscores the importance to outer retinal health of coenzyme Q oxidation in the RPE and identifies a metabolic network critical for photoreceptor survival in the context of RPE mitochondrial dysfunction.

2024-06-01·Bioresource Technology

Mitochondrial alternative oxidase pathway accelerates non-motile cell germination by enhancing respiratory carbon metabolism and maintaining redox poise in Haematococcus pluvialis

Article

作者: Yu, Wenjie ; Chen, Feng ; Zhang, Mengjie ; Li, Jing ; Zhang, Litao ; Liu, Jianguo

Low efficiency of the cultivation process is a major obstacle in the commercial production of Haematococcus pluvialis. Germination of red, non-motile cells is an efficient strategy for rapid acquisition of zoospores. However, the regulatory mechanisms associated with germination remain unexplored. In the present study, it was confirmed that the mitochondrial alternative oxidase (AOX) pathway accelerates H. pluvialis cell germination, and the regulatory mechanisms were clarified. When the AOX pathway was inhibited, the transcriptomic and metabonomic data revealed a downregulation in respiratory carbon metabolism and nucleotide synthesis due to NADH accumulation. This observation suggested that AOX promoted the rapid consumption of NADH, which accelerated carbohydrate and lipid catabolism, thereby producing carbon skeletons for DNA replication through respiratory metabolism. Moreover, AOX could potentially enhance germination by disturbing the abscisic acid signaling pathway. These findings provide novel insights for developing industrial cultivation models based on red-cell-germination for achieving rapid proliferation of H. pluvialis.