Mcp1 and Mcp2, two novel proteins involved in mitochondrial lipid homeostasis

Abstract

SummaryThe yeast mitochondrial outer membrane (MOM) protein Mdm10 is involved in at least three different processes: (1) association of mitochondria with the endoplasmic reticulum and mitochondrial lipid homeostasis (2) membrane assembly of MOM proteins, and (3) inheritance and morphogenesis of mitochondria. To decipher the precise role of Mdm10 in mitochondrial function, we screened for high-copy suppressors of the severe growth defect of the mdm10D mutant. We identified two novel mitochondrial proteins (open reading frames YOR228c and YLR253w) that we named Mdm10 complementing protein (Mcp) 1 and Mcp2. Overexpression of Mcp1 or Mcp2 restores the alterations in morphology and stability of respiratory chain complexes of mitochondria devoid of Mdm10, but the observed defect in assembly of MOM proteins is not rescued. Lipid analysis demonstrates that elevated levels of Mcp1 and Mcp2 restore the alterations in mitochondrial phospholipid and ergosterol homeostasis in cells lacking Mdm10. Collectively, this work identifies two novel proteins that play a role in mitochondrial lipid homeostasis and describes a role of Mdm10 in ergosterol trafficking.

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

“…Multicopy extragenic suppressors of phenotypes associated with loss of ERMES components have recently been identified (104). Specifically, a multicopy suppressor screen for genes whose increased dose could restore growth of mdm10 cells on a nonfermentable carbon source at 37°C led to the isolation of two mitochondrial proteins, Mdm10 complementing protein (Mcp)1 and Mcp2 (104).…”

“…Specifically, a multicopy suppressor screen for genes whose increased dose could restore growth of mdm10 cells on a nonfermentable carbon source at 37°C led to the isolation of two mitochondrial proteins, Mdm10 complementing protein (Mcp)1 and Mcp2 (104). The overexpression of these proteins reverted the globular mitochondrial morphology of mdm10 ERMES core complex, Mdm10, is a mitochondrial -barrel protein.…”

“…Mcp1 and Mcp2 overexpression alleviated the growth defect on nonfermentable carbon source for loss-of-function mutants of the core ERMES complex (mdm12, mdm34, and mmm1). In addition, the combined absence of either Mcp1 or Mcp2 with any of the ERMES components resulted in severe growth defects (104). Although the precise molecular function of these two proteins is not known, evidence suggests that they are involved in alternative redundant function with ERMES.…”

Mitochatting – If only we could be a fly on the cell wall

“…Therefore, sterols are an additional group of lipids that might be transferred through the ER-mitochondria contact site. In support of this notion, loss of ERMES components Mdm10, Mdm12 or Mmm1 resulted in an increase of mitochondrial ergosterol levels, suggesting a connection between this contact site and ergosterol transfer to or from mitochondria [19]. Indeed, Lam6, which is localized to ERMES contact sites, was suggested to have a role in sterol transfer between the two organelles, as it was able to extract sterols from membranes [14,15].…”

Mitochondrial lipid transport at a glance

“…It has been reported that yeast cells lacking the ERMES complex have reduced ergosterol levels in mitochondria, pointing to a role of ER-mitochondria contacts for ergosterol exchange (Tan et al, 2013). Non-vesicular transport of cholesterol mediated by protein-protein interactions between lipid droplets and mitochondria has been observed in steroidogenic cells (Boström et al, 2007;Goodman, 2008;Murphy et al, 2009;Zehmer et al, 2009), but it remains unknown how contacts between lipid droplets and mitochondria are maintained.…”