High impact information on MGM1

• Our data indicate that mitochondrial membrane remodelling is regulated by cleavage of Mgm1p and show that intramembrane proteolysis by rhomboids controls cellular processes other than signalling [1].
• Deletion of MGM1 shows that aside from its role in the mitochondrion, the gene has no essential cellular function [2].
• Mgm1p is a conserved dynamin-related GTPase required for fusion, morphology, inheritance, and the genome maintenance of mitochondria in Saccharomyces cerevisiae [3].
• We show that near its NH2 terminus Mgm1 contains two conserved hydrophobic segments of which the more COOH-terminal one is cleaved by Pcp1 [4].
• Specifically, mutations in MGM1 cause mitochondrial fragmentation and a loss of mitochondrial DNA that are suppressed by abolishing DNM1-dependent fission [5].

Biological context of MGM1

• Examination of mitochondrial morphology in mgm1 cells indicates that fragmentation of mitochondrial reticuli is the primary phenotype associated with loss of MGM1 function, with secondary aggregation of mitochondrial fragments [6].
• Here, we show that mitochondrial fragmentation and mitochondrial genome loss caused by lesions in MGM1 are suppressed by three novel mutations, gag1, gag2, and gag3 (for glycerol-adapted growth) [7].
• The previously published nucleotide sequences are in perfect agreement with our sequence except for STE4 and MGM1 [8].
• The MGM1 gene is located on the right arm of chromosome XV between STE4 and PTP2 [9].
• These results indicate that Mgm1p is a mitochondrial inheritance and morphology component that functions on the mitochondrial surface [10].

Anatomical context of MGM1

• Like fzo1 and ugo1 mutants, cells disrupted for the MGM1 gene contain numerous mitochondrial fragments instead of the few long, tubular organelles seen in wild-type cells [11].
• Fragmentation of mitochondria in mgm1 mutants is rescued by disrupting DNM1, a gene required for mitochondrial division [11].
• Furthermore, we show that mgm1 mutants fail to fuse both their mitochondrial outer and inner membranes [11].
• In zygotes formed by mating mgm1 mutants, mitochondria do not fuse and mix their contents [11].

Regulatory relationships of MGM1

• Our results raise the possibility that Mgm1p regulates fusion of the mitochondrial outer membrane through its interactions with Fzo1p and Ugo1p [11].

Other interactions of MGM1

• This mgm1 phenotype is identical to that observed in cells with a conditional mutation in FZO1, which encodes a transmembrane GTPase required for mitochondrial fusion, raising the possibility that Mgm1p is also required for fusion [6].
• Limited proteolysis of the large isoform by the mitochondrial rhomboid protease Pcp1/Rbd1 generates the short isoform of Mgm1 but how this is regulated is unclear [4].
• We show that Mgm1p serves as an upstream regulator of Tim11p protein stability, ATP synthase assembly, cristae morphology and cytochrome c storage within cristae [12].

Analytical, diagnostic and therapeutic context of MGM1

• Electron microscopy demonstrates that although mgm1 mutants display aberrant mitochondrial inner membrane cristae, mgm1 dnm1 double mutants restore normal inner membrane structures [11].

References