Abstract
The endoplasmic reticulum mitochondria encounter structure (ERMES) tethers the ER to mitochondria and contains four structural components: Mmm1, Mdm12, Mdm10, and Mmm2 (Mdm34). The Gem1 protein may play a role in regulating ERMES function. Saccharomyces cerevisiae and Neurospora crassa strains lacking any of Mmm1, Mdm12, or Mdm10 are known to show a variety of phenotypic defects including altered mitochondrial morphology and defects in the assembly of β-barrel proteins into the mitochondrial outer membrane. Here we examine ERMES complex components in N. crassa and show that Mmm1 is an ER membrane protein containing a Cys residue near its N-terminus that is conserved in the class Sordariomycetes. The residue occurs in the ER-lumen domain of the protein and is involved in the formation of disulphide bonds that give rise to Mmm1 dimers. Dimer formation is required for efficient assembly of Tom40 into the TOM complex. However, no effects are seen on porin assembly or mitochondrial morphology. This demonstrates a specificity of function and suggests a direct role for Mmm1 in Tom40 assembly. Mutation of a highly conserved region in the cytosolic domain of Mmm1 results in moderate defects in Tom40 and porin assembly, as well as a slight morphological phenotype. Previous reports have not examined the role of Mmm2 with respect to mitochondrial protein import and assembly. Here we show that absence of Mmm2 affects assembly of β-barrel proteins and that lack of any ERMES structural component results in defects in Tom22 assembly. Loss of N. crassa Gem1 has no effect on the assembly of these proteins but does affect mitochondrial morphology.
Highlights
Regions of close apposition between the endoplasmic reticulum (ER) and mitochondria have been observed for several years and are thought to be required for lipid and calcium exchange between the two organelles [1,2,3,4,5,6]
The Mmm1 protein was originally characterized as a mitochondrial outer membrane (MOM) protein in both S. cerevisiae and N. crassa [16,17,22,24,33,51]
More recent studies in S. cerevisiae have concluded that the protein resides in the ER membrane and associates with mitochondrial outer membrane proteins to form the ER-mitochondria encounter structure (ERMES) [9,11,12]
Summary
Regions of close apposition between the endoplasmic reticulum (ER) and mitochondria have been observed for several years and are thought to be required for lipid and calcium exchange between the two organelles [1,2,3,4,5,6]. Interactions between proteins in the ER membrane and the outer mitochondrial membrane that could act as tethers between the two organelles have been described. In the second, ERlocalized Mfn tethers mitochondria to the ER by homotypic and heterotypic interactions with mitochondrially localized Mfn or Mfn1 [8]. In Saccharomyces cerevisiae the ER-mitochondria encounter structure (ERMES) has been shown to tether the two organelles [9,10]. The ERMES is composed of four interacting structural proteins: the ER membrane protein, Mmm; two mitochondrial outer membrane (MOM) proteins, Mmm (Mdm34) and Mdm; and the cytosolic bridge protein, Mdm. The Gem protein has been reported to co-purify with the ERMES and it may play a role in regulating the size, organization, and function of the complex [11,12]. A different study concluded that Gem is not involved in ERMES assembly or maintenance [10]
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