Mitochondria fuse through a coordinated process involving distinct proteins that mediate the fusion of the outer and inner mitochondrial membranes.
Mitochondrial fusion is essential for maintaining mitochondrial health and function. This process involves two distinct steps: fusion of the outer mitochondrial membrane (OMM) and fusion of the inner mitochondrial membrane (IMM). Different proteins mediate these steps.
Outer Mitochondrial Membrane Fusion
- Mediators: In mammals, the fusion of the outer mitochondrial membrane (OMM) is primarily mediated by two dynamin-related GTPases: Mitofusin 1 (Mfn1) and Mitofusin 2 (Mfn2). These proteins are anchored in the OMM.
- Mechanism: Mfn1 and Mfn2 on adjacent mitochondria interact with each other, forming a complex that facilitates membrane tethering and subsequent fusion. GTP hydrolysis provides the energy required for this process.
Inner Mitochondrial Membrane Fusion
- Mediator: Fusion of the inner mitochondrial membrane (IMM) is primarily mediated by a dynamin-related GTPase called Optic atrophy 1 (Opa1) in mammals.
- Mechanism: Opa1 exists in both long (L-Opa1) and short (S-Opa1) forms. L-Opa1 is membrane-bound and plays a critical role in IMM fusion. The exact mechanism is still under investigation, but it involves membrane tethering, lipid mixing, and GTP hydrolysis to drive the fusion event. Both L-Opa1 and S-Opa1 are required for efficient fusion.
In summary, mitochondrial fusion is a two-step process involving Mfn1 and Mfn2 for outer membrane fusion and Opa1 for inner membrane fusion, all requiring GTP hydrolysis.
