Most cited article - PubMed ID 37279941
A Novel Group of Dynamin-Related Proteins Shared by Eukaryotes and Giant Viruses Is Able to Remodel Mitochondria From Within the Matrix
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.
- Keywords
- Mgm1, Opa1, apoptosis, cristae, dynamin‐related protein, membrane remodelling, mitochondrial dynamics, phylogeny,
- MeSH
- Membrane Fusion * physiology MeSH
- Fungi * physiology MeSH
- Mitochondrial Dynamics * physiology MeSH
- Mitochondrial Membranes * physiology MeSH
- Mitochondrial Proteins metabolism genetics MeSH
- Mitochondria * physiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Mitochondrial Proteins MeSH