主要目的：评估艾地苯醌片用于治疗Leber’s遗传性视神经病变（LHON）患者的视觉障碍的临床有效性（与安慰剂相比）。临床有效性的评价基于第52周BCVA与基线相比达到CRR（即，与基线相比，视标内BCVA改善≥0.2 logMAR，视标外BCVA≤1.6 logMAR）的受试者比例。次要目的：评估艾地苯醌在Leber’s遗传性视神经病变（LHON）患者中的安全性。

开始日期2022-07-13

申办/合作机构

齐鲁制药有限公司

NCT05411978 / Recruiting临床4期IIT

A Multi-center, Randomized, Double-blind, Placebo-controlled Parallel Pilot Study to Evaluate Safety and Efficacy of Oral Idebenone for Preventive Treatment of Migraine in Adult Migraine Patients

This is a multi-center, prospective, double-blind randomized controlled trial on a sample of patients with migraine. Subjects will only be enrolled when a physician or research assistant who is familiar with the study protocol is available to enroll patients. Written, informed consent will be obtained from each patient. Consent will include a discussion of the risks and benefits.

开始日期2022-05-09

申办/合作机构

北京天坛医院

ChiCTR2200059044 / Suspended临床3期IIT

The efficacy and safety of Idebenone Tablets on Leber’s Hereditary Optic Neuropathy, LHON: A randomized, double-blind,placebo parallel controlled clinical trial

开始日期2022-05-01

申办/合作机构-

100 项与 Electron transport chain complex proteins 相关的临床结果

登录后查看更多信息

100 项与 Electron transport chain complex proteins 相关的转化医学

登录后查看更多信息

0 项与 Electron transport chain complex proteins 相关的专利（医药）

登录后查看更多信息

项与 Electron transport chain complex proteins 相关的文献（医药）

2024-07-31·Science Translational Medicine

MGA deletion leads to Richter’s transformation by modulating mitochondrial OXPHOS

Article

作者: Danilov, Alexey ; Liu, Tingting ; Zhang, Bo ; Remke, Marianne ; Zhang, Jibin ; Chan, Wing C ; Jia, Zhenyu ; Buchner, Maike ; Hart, Kevyn ; Wang, Xuesong ; Song, Joo ; Iyer, Prajish ; Venkataraman, Girish ; Jin, Meiling ; Rosen, Steven T ; Siegert, Viola ; Siddiqi, Tanya ; Wang, Lili ; Yu, Lei

Richter’s transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. MGA ( Max gene associated ), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms of MGA deletion that drive CLL to RT remain elusive. We established an RT mouse model by knockout of Mga in the Sf3b1 / Mdr CLL model using CRISPR-Cas9 to determine the role of Mga in RT. Murine RT cells exhibited mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). Through RNA sequencing and functional characterization, we identified Nme1 (nucleoside diphosphate kinase) as an Mga target, which drives RT by modulating OXPHOS. Given that NME1 is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and electron transport chain complex II substantially prolongs the survival of RT mice in vivo. Our results suggest that the Mga-Nme1 axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a potential therapeutic avenue for RT.

2024-06-01·Journal of Dairy Science

Diacylglycerol O-acyltransferase (DGAT) isoforms play a role in peridroplet mitochondrial fatty acid metabolism in bovine liver

Article

作者: Fan, Wenwen ; Xu, Chuang ; Loor, Juan J ; Tian, Yan ; Aernouts, Ben ; Wang, Shuang ; Zhang, Bingbing ; Chang, Yaqi ; Mauck, John ; Yang, Tianjiao ; Xie, Meng ; Yang, Wei

Hepatocellular lipid accumulation characterizes fatty liver in dairy cows. Lipid droplets (LD), specialized organelles that store lipids and maintain cellular lipid homeostasis, are responsible for the ectopic storage of lipids associated with several metabolic disorders. In recent years, non-ruminant studies have reported that LD-mitochondria interactions play an important role in lipid metabolism. Due to the role of diacylglycerol acyltransferase isoforms (DGAT1 and DGAT2) in LD synthesis, we explored mechanisms of mitochondrial fatty acid transport in ketotic cows using liver biopsies and isolated primary hepatocytes. Compared with healthy cows, cows with fatty liver had massive accumulation of LD and high protein expression of the triglyceride (TAG) synthesis-related enzymes DGAT1 and DGAT2, LD synthesis-related proteins perilipin 2 (PLIN2) and perilipin 5 (PLIN5), and the mitochondrial fragmentation-related proteins dynamin-related protein 1 (DRP1) and fission 1 (FIS1). In contrast, factors associated with fatty acid oxidation, mitochondrial fusion and mitochondrial electron transport chain complex were lower compared with those in the healthy cows. In addition, transmission electron microscopy revealed significant contacts between LD-mitochondria in liver tissue from cows with fatty liver. Compared with isolated cytoplasmic mitochondria, expression of carnitine palmitoyl transferase 1A (CPT1A) and DRP1 was lower, but mitofusin 2 (MFN2) and mitochondrial electron transport chain complex was greater in isolated peridroplet mitochondria from hepatic tissue of cows with fatty liver. In vitro data indicated that exogenous free fatty acids (FFA) induced hepatocyte LD synthesis and mitochondrial dynamics consistent with in vivo results. Furthermore, DGAT2 inhibitor treatment attenuated the FFA-induced upregulation of PLIN2 and PLIN5 and rescued the impairment of mitochondrial dynamics. Inhibition of DGAT2 also restored mitochondrial membrane potential and reduced hepatocyte reactive oxygen species production. The present in vivo and in vitro results indicated there are functional differences among different types of mitochondria in the liver tissue of dairy cows with ketosis. Activity of DGAT2 may play a key role in maintaining liver mitochondrial function and lipid homeostasis in dairy cows during the transition period.

2024-05-31·PNAS Nexus

Hyperbaric oxygen treatment reveals spatiotemporal OXPHOS plasticity in the porcine heart

Article

作者: Cabrera-Orefice, Alfredo ; Petersen, Bjoern ; Tomczak, Jan-Niklas ; Szibor, Marten ; Pohjoismäki, Jaakko L O ; Heyne, Estelle ; Henze, Dirk ; Wittig, Ilka ; Heidler, Juliana

AbstractCardiomyocytes meet their high ATP demand almost exclusively by oxidative phosphorylation (OXPHOS). Adequate oxygen supply is an essential prerequisite to keep OXPHOS operational. At least two spatially distinct mitochondrial subpopulations facilitate OXPHOS in cardiomyocytes, i.e. subsarcolemmal (SSM) and interfibrillar mitochondria (IFM). Their intracellular localization below the sarcolemma or buried deep between the sarcomeres suggests different oxygen availability. Here, we studied SSM and IFM isolated from piglet hearts and found significantly lower activities of electron transport chain enzymes and F1FO-ATP synthase in IFM, indicative for compromised energy metabolism. To test the contribution of oxygen availability to this outcome, we ventilated piglets under hyperbaric hyperoxic (HBO) conditions for 240 min. HBO treatment raised OXPHOS enzyme activities in IFM to the level of SSM. Complexome profiling analysis revealed that a high proportion of the F1FO-ATP synthase in the IFM was in a disassembled state prior to the HBO treatment. Upon increased oxygen availability, the enzyme was found to be largely assembled, which may account for the observed increase in OXPHOS complex activities. Although HBO also induced transcription of genes involved in mitochondrial biogenesis, a full proteome analysis revealed only minimal alterations, meaning that HBO-mediated tissue remodeling is an unlikely cause for the observed differences in OXPHOS. We conclude that a previously unrecognized oxygen-regulated mechanism endows cardiac OXPHOS with spatiotemporal plasticity that may underlie the enormous metabolic and contractile adaptability of the heart.