Mazzen H. Eldeeb, Lizeth J. Camacho Lopez, Flavia Fontanesi
The functional and structural relationship among the individual components of the mitochondrial respiratory chain constitutes a central aspect of our understanding of aerobic catabolism. This interplay has been a subject of intense debate for over 50 years. It is well established that individual respiratory enzymes associate into higher-order structures known as respiratory supercomplexes, which represent the evolutionarily conserved organizing principle of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, supercomplexes are formed by a complex III homodimer flanked by one or two complex IV monomers, and their high-resolution structures have been recently elucidated. Despite the wealth of structural information, several proposed supercomplex functions remain speculative and our understanding of their physiological relevance is still limited. Recent advances in the field were made possible by the construction of yeast strains where the association of complex III and IV into supercomplexes is impeded, leading to diminished respiratory capacity and compromised cellular competitive fitness. Here, we discuss the experimental evidence and hypotheses relative to the functional roles of yeast respiratory supercomplexes. Moreover, we review the current models of yeast complex III and IV assembly in the context of supercomplex formation and highlight the data scattered throughout the literature suggesting the existence of cross talk between their biogenetic processes.
线粒体呼吸链各个组成部分之间的功能和结构关系是我们了解有氧分解代谢的一个核心方面。50 多年来,这种相互作用一直是激烈争论的主题。目前已经明确的是,单个呼吸酶结合成称为呼吸超级复合物的高阶结构,这代表了线粒体呼吸链在进化过程中保守的组织原则。在酿酒酵母中,超级复合物由一个复合体 III 同二聚体和一个或两个复合体 IV 单体组成,其高分辨率结构最近已被阐明。尽管结构信息丰富,但一些拟议的超级复合体功能仍是猜测性的,我们对其生理相关性的了解仍然有限。该领域的最新进展得益于酵母菌株的构建,在这种菌株中,复合体 III 和 IV 与超级复合体的结合受到阻碍,从而导致呼吸能力下降和细胞竞争能力受损。在此,我们将讨论与酵母呼吸超级复合体的功能作用有关的实验证据和假设。此外,我们还回顾了在超级复合物形成背景下酵母复合物 III 和 IV 组装的现有模型,并强调了散见于文献中的数据,这些数据表明它们的生物遗传过程之间存在交叉作用。
{"title":"Mitochondrial respiratory supercomplexes of the yeast Saccharomyces cerevisiae","authors":"Mazzen H. Eldeeb, Lizeth J. Camacho Lopez, Flavia Fontanesi","doi":"10.1002/iub.2817","DOIUrl":"10.1002/iub.2817","url":null,"abstract":"<p>The functional and structural relationship among the individual components of the mitochondrial respiratory chain constitutes a central aspect of our understanding of aerobic catabolism. This interplay has been a subject of intense debate for over 50 years. It is well established that individual respiratory enzymes associate into higher-order structures known as respiratory supercomplexes, which represent the evolutionarily conserved organizing principle of the mitochondrial respiratory chain. In the yeast <i>Saccharomyces cerevisiae</i>, supercomplexes are formed by a complex III homodimer flanked by one or two complex IV monomers, and their high-resolution structures have been recently elucidated. Despite the wealth of structural information, several proposed supercomplex functions remain speculative and our understanding of their physiological relevance is still limited. Recent advances in the field were made possible by the construction of yeast strains where the association of complex III and IV into supercomplexes is impeded, leading to diminished respiratory capacity and compromised cellular competitive fitness. Here, we discuss the experimental evidence and hypotheses relative to the functional roles of yeast respiratory supercomplexes. Moreover, we review the current models of yeast complex III and IV assembly in the context of supercomplex formation and highlight the data scattered throughout the literature suggesting the existence of cross talk between their biogenetic processes.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"485-504"},"PeriodicalIF":3.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara M. Elgendy, Dana M. Zaher, Nadin H. Sarg, Nour N. Abu Jayab, Dima W. Alhamad, Taleb H. Al-Tel, Hany A. Omar
Hepatocellular carcinoma (HCC) significantly contributes to cancer-related mortality due to the limited response of HCC to current anticancer therapies, thereby necessitating more effective treatment approaches. Energy restriction mimetic agents (ERMAs) have emerged as potential therapies in targeting the Warburg effect, a unique metabolic process in cancer cells. However, ERMAs exhibit limited efficacy when used as monotherapy. Additionally, ERMAs have been found to induce autophagy in cancer cells. The role of autophagy in cancer survival remains a subject of debate. Thus, it is crucial to ascertain whether ERMA-induced autophagy is a mechanism for cell survival or cell death in HCC. Our study aims to investigate the effect of autophagy inhibition on the survival of HCC cells treated with ERMAs while also examining the potential of combining an autophagy inhibitor such as spautin-1 with ERMAs to enhance HCC cell death. Our results suggest a cytoprotective role for ERMA-induced autophagy in HCC cells, as combining the autophagy inhibitor spautin-1 with ERMAs effectively suppressed ERMA-induced autophagy and synergistically enhanced their antitumor activity. The treatment combination promoted HCC death through apoptosis, cell cycle arrest, and inhibition of AKT and ERK activation, which are known to play a key role in cellular proliferation. Collectively, our findings highlight a potential strategy to combat HCC by combining energy restriction with autophagy inhibition.
{"title":"Autophagy inhibition potentiates energy restriction-induced cell death in hepatocellular carcinoma cells","authors":"Sara M. Elgendy, Dana M. Zaher, Nadin H. Sarg, Nour N. Abu Jayab, Dima W. Alhamad, Taleb H. Al-Tel, Hany A. Omar","doi":"10.1002/iub.2816","DOIUrl":"10.1002/iub.2816","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) significantly contributes to cancer-related mortality due to the limited response of HCC to current anticancer therapies, thereby necessitating more effective treatment approaches. Energy restriction mimetic agents (ERMAs) have emerged as potential therapies in targeting the Warburg effect, a unique metabolic process in cancer cells. However, ERMAs exhibit limited efficacy when used as monotherapy. Additionally, ERMAs have been found to induce autophagy in cancer cells. The role of autophagy in cancer survival remains a subject of debate. Thus, it is crucial to ascertain whether ERMA-induced autophagy is a mechanism for cell survival or cell death in HCC. Our study aims to investigate the effect of autophagy inhibition on the survival of HCC cells treated with ERMAs while also examining the potential of combining an autophagy inhibitor such as spautin-1 with ERMAs to enhance HCC cell death. Our results suggest a cytoprotective role for ERMA-induced autophagy in HCC cells, as combining the autophagy inhibitor spautin-1 with ERMAs effectively suppressed ERMA-induced autophagy and synergistically enhanced their antitumor activity. The treatment combination promoted HCC death through apoptosis, cell cycle arrest, and inhibition of AKT and ERK activation, which are known to play a key role in cellular proliferation. Collectively, our findings highlight a potential strategy to combat HCC by combining energy restriction with autophagy inhibition.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"577-588"},"PeriodicalIF":3.7,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retraction: ‘ miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition of the cell cycle and the epithelial to mesenchymal transition in cervical cancer cells’ by Jian-Li Zhao, Le Zhang, Xu Guo, Jing-Hua Wang, Wen Zhou, Min Liu, Xin Li and Hua Tang, IUBMB Life2015, 67, 380–394