Hashimi Hassan, Gahura Ondřej, Pánek Tomáš
Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Branišovská 31, České Budějovice, 370 05, Czechia.
Department of Molecular Biology and Genetics, Faculty of Science, University of South Bohemia, Branišovská 31, České Budějovice, 370 05, Czechia.
Biol Rev Camb Philos Soc. 2025 Apr;100(2):920-935. doi: 10.1111/brv.13168. Epub 2024 Nov 18.
Mitochondria are dynamic and plastic, undergoing continuous fission and fusion and rearrangement of their bioenergetic sub-compartments called cristae. These fascinating processes are best understood in animal and fungal models, which are taxonomically grouped together in the expansive Opisthokonta supergroup. In opisthokonts, crista remodelling and inner membrane fusion are linked by dynamin-related proteins (DRPs). Animal Opa1 (optical atrophy 1) and fungal Mgm1 (mitochondrial genome maintenance 1) are tacitly considered orthologs because their similar mitochondria-shaping roles are mediated by seemingly shared biochemical properties, and due to their presence in the two major opisthokontan subdivisions, Holozoa and Holomycota, respectively. However, molecular phylogenetics challenges this notion, suggesting that Opa1 and Mgm1 likely had separate, albeit convergent, evolutionary paths. Herein, we illuminate disparities in proteolytic processing, structure, and interaction network that may have bestowed on Opa1 and Mgm1 distinct mechanisms of membrane remodelling. A key disparity is that, unlike Mgm1, Opa1 directly recruits the mitochondrial phospholipid cardiolipin to remodel membranes. The differences outlined herein between the two DRPs could have broader impacts on mitochondrial morphogenesis. Outer and inner membrane fusion are autonomous in animals, which may have freed Opa1 to repurpose its intrinsic activity to remodel cristae, thereby regulating the formation of respiratory chain supercomplexes. More significantly, Opa1-mediated crista remodelling has emerged as an integral part of cytochrome c-regulated apoptosis in vertebrates, and perhaps in the cenancestor of animals. By contrast, outer and inner membrane fusion are coupled in budding yeast. Consequently, Mgm1 membrane-fusion activity is inextricable from its role in the biogenesis of fungal lamellar cristae. These disparate mitochondrial DRPs ultimately may have contributed to the different modes of multicellularity that have evolved within Opisthokonta.
线粒体具有动态性和可塑性，其生物能量亚区室（称为嵴）会持续进行裂变、融合和重排。这些迷人的过程在动物和真菌模型中得到了最好的理解，动物和真菌在广阔的后鞭毛生物超群中被分类在一起。在后鞭毛生物中，嵴重塑和内膜融合由动力蛋白相关蛋白（DRP）连接。动物的视神经萎缩蛋白1（Opa1）和真菌的线粒体基因组维持蛋白1（Mgm1）被默认认为是直系同源物，因为它们类似的线粒体塑造作用是由看似共同的生化特性介导的，并且由于它们分别存在于后鞭毛生物的两个主要分支——全动物亚界和全真菌亚界中。然而，分子系统发育学对这一概念提出了挑战，表明Opa1和Mgm1可能有独立的、尽管是趋同的进化路径。在此，我们阐明了蛋白水解加工、结构和相互作用网络方面的差异，这些差异可能赋予了Opa1和Mgm1不同的膜重塑机制。一个关键的差异是，与Mgm1不同，Opa1直接招募线粒体磷脂心磷脂来重塑膜。本文概述的两种DRP之间的差异可能对线粒体形态发生有更广泛的影响。动物的外膜和内膜融合是自主的，这可能使Opa1能够重新利用其内在活性来重塑嵴，从而调节呼吸链超复合物的形成。更重要的是，Opa1介导的嵴重塑已成为脊椎动物中细胞色素c调节的细胞凋亡的一个组成部分，也许在动物的共同祖先中也是如此。相比之下，出芽酵母中的外膜和内膜融合是耦合的。因此，Mgm1的膜融合活性与其在真菌片状嵴生物发生中的作用密不可分。这些不同的线粒体DRP最终可能促成了后鞭毛生物中进化出的不同多细胞模式。
