Molecular Mechanisms of Mitochondrial Dynamics
Membrane remodeling of mitochondria involves a set of large GTP-hydrolyzing enzymes. These mechanochemical machines assemble on the mitochondrial surface and manipulate the lipid bilayers through nucleotide-dependent conformational changes.
Mitochondrial fusion is a membrane-remodeling process that coordinately merges the outer and inner membranes between two mitochondria. It requires three large GTPases: the mitofusins Mfn1 and Mfn2, and the dynamin-related protein OPA1 (Optic Atrophy 1). Mitofusins are embedded in the mitochondrial outer membrane, whereas OPA1 is associated with the inner membrane. We have shown that mitofusins and OPA1 act at distinct steps during mitochondrial fusion: mitofusins are essential for outer membrane fusion, whereas OPA1 is required for inner membrane fusion. Loss of mitofusins or OPA1 prevents mitochondrial fusion and severely impacts mitochondrial physiology.
Mitochondrial fission requires the recruitment and assembly of the dynamin-related GTPase Drp1/Dnm1L, which constricts the diameter of mitochondria and ultimately results in scission. Drp1 is a cytosolic protein that is recruited to the mitochondrial surface via a number of mitochondrial transmembrane receptors. Mitochondrial fission affects many cellular functions, including apoptosis, programmed necrosis, mitochondrial distribution, and mitochondrial degradation by autophagy.