Mitochondria Dynamics

Mitochondria Dynamics

It has become increasingly clear that rather than existing as isolated organelles mitochondria are much more dynamic. While myocyte mitochondria do exhibit spheroid morphologies, mitochondria in other cells types have linked and filamentous-like morphology. As discussed previously mitochondria biogenesis occurs through nuclear-encoded transcription factors that instruct the cell to orchestrate synthesis of mitochondrial components to form new mitochondria. However, mitochondria are not static organelles once they are created, as they also undergo fusion and fission. For example, two existing mitochondria can fuse to generate another mitochondria. A single mitochondria can also undergo symmetrical fission to increase

These proteins are OPA, which localizes to the inner mitochondria membranes (IMM), and MFN1 and MFN2, which localize to the outer mitochondria membrane (OMM). The OMM fusion proteins MFN1 and MFN2 contain an N-terminal GTPase domain along with 2 hydrophobic heptad repeated regions HR1 and HR2 (Fig 1.8). MFN1 and MFN2, although they share 66% sequence homology, can either homo- or heterodimerize to each other via their HR domains, and believed that the latter dimerization allows for stronger tethering (88). Interestingly although OPA is dispensable for OMM tethering, it is required for establishing cristae layering and maintaining membrane potential (89). Although fusion is important to regulate network morphology, cell-type specificity requirements dictates different levels of “healthy” fragmentation that allows normal cellular

In a similar vein, in vitro study with BJAB demonstrates that endogenous Mfn2 domains interact with GTP-Ras to control the rate of proliferation of human lymphomas (108). While there is much established role of human Mfn2 mutations in the mitochondrial dynamics and pathologies to CMT2A, its role apart from CMT2A in cell line studies have suggested that it may play a much more diverse role beyond mitochondria localization. Lastly, in a model whereby mitofusin/MARF and Opa1 deficient mice both exhibited decreased mitochondrial fusion, increased ROS production, and decreased membrane polarization within cardiomyocytes, leading to reduced heart tube function, genetic reduction of ROS through SOD could rescue only the Opa1’s phenotype, but not mitofusin/MARF mutants (109). Only by reducing ER stress could the heart tube malfunction be rescued in mitofusin/MARF mutants, suggesting alternative roles mitochondrial membrane fusion proteins play in mitochondria health