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.


 

References:

Haeussler, S., A. Yeroslaviz, S.G. Rolland, S. Luehr, E.J. Lambie, and B. Conradt. (2021). Genome-wide RNAi screen for regulators of UPRmt in Caenorhabditis elegans mutants with defects in mitochondrial fusion. G3 (Bethesda). [Epub: Ahead of Print]
Zhang, Y., X. Liu, J. Bai, X. Tian, X. Zhao, W. Liu, X. Duan, W. Shang, H.Y. Fan, and C. Tong. (2016). Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuron.al Homeostasis. Mol. Cell 61: 111-124.
Examples:

TC#NameOrganismal TypeExample
8.A.167.1.1

Mitoguardin (Mtga) of 525 aas and at least one N-terminal TMS, and possibly one or two more TMSs. It is a regulator of mitochondrial fusion and is required to maintain neuronal homeostasis (Zhang et al. 2016). See TC# 1.R.1 for more details.

MIGA of Drosophila melanogaster (Fruit fly)

 
8.A.167.1.2

MitoGuArdin, Fzo-1 or Miga-1, of 499 aas and at least 1 N-terminal TMS plus as many as 5 more TMSs, one next to the N-terminal TMS, and 3 or 4 TMSs at the C-terminus. Fzo1 is involved in mitochondrial membrane fusion and fission (Haeussler et al. 2021).

Miga1 of Caenorhabditis elegans

 
8.A.167.1.3

Mitoguardin 1 (MITO1 or MITO-1 of 632 aas and 1 N-terminal TMS plus as many as four more TMSs, one next to the N-terminal TMS and as many as 4 C-terminal TMSs.  Human mitoguardin 2 is included in TC# 1.R.1.1.1.

MIGA1 of Homo sapiens

 
8.A.167.1.4

Uncharacterized protein of 497 aas with 1 or 2 N-terminal TMSs plus as many as 4 C-terminal TMSs.

UP of Salmo trutta (river trout)

 
8.A.167.1.5

Uncharacterized protein of 435 aas and at least 2 TMSs, N- and C-terminal, but possibly more near the C-terminus.

UP of Tachysurus fulvidraco (yellow catfish)