8.A.167. The Mitoguardin (MIGA) Family
Mitochondria undergo frequent morphological changes through fission and fusion. Mutations in core members of the mitochondrial fission/fusion machinery are responsible for severe neurodegenerative diseases. Zhang et al. 2016 found that the loss of mitoguardin (MIGA), leads to mitochondrial defects and neurodegeneration in fly eyes. Mammals express two orthologs of miga: Miga1 and Miga2. Both MIGA1 and MIGA2 form homotypic and heterotypic complexes on the outer membrane of the mitochondria. Loss of MIGA results in fragmented mitochondria, whereas overexpression of MIGA leads to clustering and fusion of mitochondria in both fly and mammalian cells. MIGA proteins function downstream of mitofusin (see TC#s 1.N.6.1.2 and 1.R.1) and interact with MitoPLD (see 1.R.1) to stabilize MitoPLD and facilitate MitoPLD dimer formation. Therefore, Zhang et al. 2016 proposed that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD.