Murley et al. identify a yeast protein that might coordinate the function of vacuoles and mitochondria by transferring sterols at the sites where these organelles are contacted by the ER.
The ERMES complex connects the yeast ER to mitochondria, promoting the exchange of lipids between these organelles and marking the sites of mitochondrial division. Murley et al. looked for proteins that interact with the ERMES complex and identified a previously uncharacterized ER protein called Ylr072w. The protein localized to ER–vacuole as well as ER–mitochondria contacts and was recruited to these sites by Vac8 and Tom70/71, respectively. Because Ylr072w could transfer sterols between artificial membranes in vitro, the researchers renamed it Lipid transfer at contact site 1, or Ltc1. The researchers also identified a family of related proteins, conserved from yeast to humans.
Certain environmental stresses induce the formation of ergosterol-rich domains in vacuolar membranes. Cells required Ltc1 to form these domains and, when Murley et al. increased the proportion of Ltc1 at ER–vacuole contacts, cells formed ergosterol-rich vacuole domains even in the absence of stress. The function of these membrane domains is unknown, but, because they contain components of the TORC1 signaling complex, they may control the activity of this key metabolic regulator.
Whether Ltc1 senses or alters the lipid content of mitochondria remains unclear, but the protein was required for cell viability in the absence of the ERMES complex protein Mdm34, indicating that Ltc1 separately regulates mitochondrial function. Indeed, by contacting both mitochondria and vacuoles, Ltc1 might coordinate the metabolic activities of the two organelles.
References
Author notes
Text by Ben Short
