Fis1 is an outer mitochondrial membrane protein that plays a role in mitochondrial membrane fission []. In Saccharomyces cerevisiae, it facilitates mitochondrial fission by forming protein complexes with Dnm1 and Mdv1 []. It contains tetratrico-peptide repeat (TPR)-like domain and a C-terminal transmembrane region [, ].
The mitochondrial fission protein Fis1 consists of two tetratricopeptide repeats. This entry represents the N-terminal tetratricopeptide repeat [, ]. Fis1 is an outer mitochondrial membrane protein that plays a role in mitochondrial membrane fission [].
The mitochondrial fission protein Fis1 consists of two tetratricopeptide repeats. This entry represents the C-terminal tetratricopeptide repeat [, ]. Fis1 is an outer mitochondrial membrane protein that plays a role in mitochondrial membrane fission [].
Fis1, along with Dnm1 and Mdv1, is an essential protein in mediating mitochondrial fission. Dnm1 and Fis1 are highly conserved, with a common mechanism in disparate species. In mutants of these proteins, mitochondrial fission is impaired, resulting in networks of undivided mitochondria. Fis1 appears to act via the recruitment of division complexes to the mitochondrial outer membrane. Dnm1 is recruited to mitochondria via interactions with the adaptor proteins Caf4 and Mdv1, which bind directly to Fis1 [, ].The Fis1 N terminus is cytosolic andtethered to the mitochondrial outer membrane via a C-terminal transmembrane domain. The cytosolic domain of Fis1 forms a six-helix bundle, in which the central four helices consist of two tandem tetratricopeptide repeat (TPR)-like motifs, known to mediate protein-protein interactions [, , , ].
Caf4 is a WD40 repeats containing protein involved in mitochondrial fission. It displays physical interactions with CCR4-NOT complex []. It has a paralogue, Mdv1. Both Caf4 and Mdv1 act as adapter proteins, binding to Fis1 on the mitochondrial outer membrane and recruiting the dynamin-like GTPase Dnm1 to form mitochondrial fission complexes []. However, Fis1 and Caf4, but not Mdv1, determine the polar localization of Dnm1 clusters on the mitochondrial surface [].
This entry represents mitochondrial division protein 1 (Mdv1), which is a component of the mitochondrial fission machinery in Saccharomyces cerevisiae. The protein is also involved in peroxisome proliferation []. Mdv1 along with Fis1 is also involved in controlling Dnm-1 dependent devision, a GTPase involved in the mediation of mitochondrial division. In this role, Mdv1 is the linker between Fis1 and Dnm1. Mdv1 plays a key role in the regulation of Dnm1 self-assembly [].Mdv1 has a partially redundant function to CAF4 in acting as an adapter protein, binding to FIS1 on the mitochondrial outer membrane and recruiting the dynamin-like GTPase DNM1 to form mitochondrial fission complexes. Formation of these complexes is required to promote constriction and fission of the mitochondrial compartment at a late step in mitochondrial division [, ]. Mdv1 interacts with CAF4, DNM1 and FIS1, components of the mitochondrial fission machinery. It interacts via its N-terminal, coiled-coil extension (NTE) with FIS1, and via its WD repeats with DNM1. Mdv1 is uniformly distributed on the cytoplasmic face of the mitochondrial outer membrane. This localisation is dependent on FIS1. It reorganises to punctate structures on mitochondria, corresponding to mitochondrial constriction sites, at a late step in mitochondrial division. This relocalisation is dependent on DNM1.
This entry represents the mitochondrial dynamics protein MID49/MID51. Most members of this protein family contain a Mab-21 domain and are found in chordates.In humans, MID49 and MID51 are outer membrane proteins involved in the regulation of mitochondrial organisation and required for mitochondrial fission by promoting the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. They also regulate DNM1L GTPase activity [, , , , ]. Deregulation of these proteins has been linked to human diseases such as pulmonary arterial hypertension [].
